Handbook of Experimental Pharmacology – serie

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466 produkter

Del 247 - Handbook of Experimental Pharmacology
Delta Opioid Receptor Pharmacology and Therapeutic Applications
AvEmily M. Jutkiewicz
Häftad, Engelska, 2018
1 307 kr
Skickas inom 10-15 vardagar
This volume describes our current understanding of the biological role of the delta-opioid receptor (DOR) system, focusing on its unique mechanisms of receptor trafficking and signaling in disease states. Part 1 covers the endogenous ligands that regulate the DOR system as well as novel compounds and therapies used to modulate the DOR system. Part 2 describes new insights into the localization and trafficking of the DOR and how ligand-directed signaling alters the fate of the receptor. Part 3 concentrates on the potential role of the DOR system in disease states, such as pain, mood, addiction, and Parkinson’s disease. Throughout the book, the DOR system as a target for drug development will be discussed.
Del 246 - Handbook of Experimental Pharmacology
Voltage-gated Sodium Channels: Structure, Function and Channelopathies
AvMohamed Chahine
Häftad, Engelska, 2019
1 702 kr
Skickas inom 10-15 vardagar
This book provides a timely state-of-the-art overview of voltage-gated sodium channels, their structure-function, their pharmacology and related diseases. Among the topics discussed are the structural basis of Na+ channel function, methodological advances in the study of Na+ channels, their pathophysiology and drugs and toxins interactions with these channels and their associated channelopathies.
Del 249 - Handbook of Experimental Pharmacology
Mechanisms of Drug Resistance in Cancer Therapy
AvMario Mandalà,Emanuela Romano
Inbunden, Engelska, 2019
1 702 kr
Skickas inom 10-15 vardagar
A major objective of this book is to reveal unprecedented opportunities to understand and overcome drug resistance through the clinical assessment of rational therapeutic drug combinations and the use of predictive and prognostic biomarkers to enable patient stratification and tailor treatments. It offers to the readers an updated overview on the possible reasons of failure of new and promising therapeutic opportunities.
Del 251 - Handbook of Experimental Pharmacology
Brown Adipose Tissue
AvAlexander Pfeifer,Martin Klingensporm. fl.
Inbunden, Engelska, 2019
2 267 kr
Skickas inom 10-15 vardagar
The main focus of this book is on brown adipose tissue and its metabolic function. The book provides a timely update on the latest research and shows where the field is heading. Brown adipose tissue (BAT) dissipates energy and has received considerable attention in the last few years, having been re-discovered in adult humans in 2007/9. Moreover, BAT might offer a target for novel therapies to address obesity, a health condition that has reached pandemic dimensions.
Del 252 - Handbook of Experimental Pharmacology
New Psychoactive Substances
Pharmacology, Clinical, Forensic and Analytical Toxicology
AvHans H. Maurer,Simon D. Brandt
Inbunden, Engelska, 2019
1 928 kr
Skickas inom 10-15 vardagar
This volume is designed to feature the pharmacology of new psychoactive substances, legislative aspects, information exchange including epidemiology, and clinical, forensic, and analytical toxicology in order to facilitate the understanding of this complex and rapidly developing phenomenon.
Antidepressants
From Biogenic Amines to New Mechanisms of Action
AvMatthew Macaluso,Sheldon H. Preskorn
Inbunden, Engelska, 2019
1 702 kr
Skickas inom 10-15 vardagar
This volume reviews the known neurobiology of depression and combines classic data on antidepressant treatments with modern theory on the physiology of depression. It also discusses novel mechanism of action drugs.
Sleep-Wake Neurobiology and Pharmacology
AvHans-Peter Landolt,Derk-Jan Dijk
Inbunden, Engelska, 2019
1 702 kr
Skickas inom 10-15 vardagar
This volume connects current ideas and concepts about sleep functions and circadian rhythms with the search for novel target-selective sleep-wake therapeutics. To do so, it provides a timely, state-of-the-art overview of sleep-wake mechanisms in health and disease, ongoing developments in drug discovery, and their prospects for the clinical treatment of sleep-disordered patients. It particularly focuses on the concept that sleep and wakefulness mutually affect each other, and the future therapeutic interventions with either sleep- or wake-promoting agents that are expected to not only improve the quality of sleep but also the waking behavior, cognition, mood and other sleep-associated physiological functions.The chapter 'Sleep Physiology, Circadian Rhythms, Waking Performance and the Development of Sleep-Wake Therapeutics' available open access under a CC BY 4.0 license at link.springer.com
Del 254 - Handbook of Experimental Pharmacology
Nociceptin/Orphanin FQ Peptide Receptor
AvMei-Chuan Ko,Girolamo Caló
Inbunden, Engelska, 2019
1 702 kr
Skickas inom 10-15 vardagar
The aim of this book is not only to introduce readers with a broad spectrum of biological actions of the NOP receptor, but also to feature a detailed look at the N/OFQ-NOP receptor system, medicinal chemistry, pharmacology, and clinical data of NOP-targeted ligands. This special volume book - for the first time focusing on the NOP receptor - is designed to serve as a useful reference, stimulate more research on the N/OFQ-NOP receptor system, and lead to more development of NOP-related ligands for several therapeutic applications.
Del 254 - Handbook of Experimental Pharmacology
Nociceptin/Orphanin FQ Peptide Receptor
AvMei-Chuan Ko,Girolamo Caló
Häftad, Engelska, 2020
1 702 kr
Skickas inom 10-15 vardagar
The aim of this book is not only to introduce readers with a broad spectrum of biological actions of the NOP receptor, but also to feature a detailed look at the N/OFQ-NOP receptor system, medicinal chemistry, pharmacology, and clinical data of NOP-targeted ligands. This special volume book - for the first time focusing on the NOP receptor - is designed to serve as a useful reference, stimulate more research on the N/OFQ-NOP receptor system, and lead to more development of NOP-related ligands for several therapeutic applications.
Del 255 - Handbook of Experimental Pharmacology
Calcitonin Gene-Related Peptide (CGRP) Mechanisms
Focus on Migraine
AvSusan D. Brain,Pierangelo Geppetti
Inbunden, Engelska, 2019
1 476 kr
Skickas inom 10-15 vardagar
This book is designed to focus on the role of Calcitonin Gene-Related Peptide (CGRP) in health and disease. This peptide, originally discovered in the 1980s as a sensory neuropeptide with cardiovascular effects, is now known to play a distinct role in the pain processing of migraine. The various chapters address the origin, localization and function of CGRP and its receptor in the peripheral nervous system, in the cardiovascular system, and in other tissues and organs. Further attention is paid to the drug discovery pathway where recent findings show the beneficial effect of small molecule antagonists of the CGRP receptors for the relief of the migraine attack and of monoclonal antibodies against CGRP or the CGRP receptor for migraine prevention.
Del 255 - Handbook of Experimental Pharmacology
Calcitonin Gene-Related Peptide (CGRP) Mechanisms
Focus on Migraine
AvSusan D. Brain,Pierangelo Geppetti
Häftad, Engelska, 2020
1 137 kr
Skickas inom 10-15 vardagar
This book is designed to focus on the role of Calcitonin Gene-Related Peptide (CGRP) in health and disease. This peptide, originally discovered in the 1980s as a sensory neuropeptide with cardiovascular effects, is now known to play a distinct role in the pain processing of migraine. The various chapters address the origin, localization and function of CGRP and its receptor in the peripheral nervous system, in the cardiovascular system, and in other tissues and organs. Further attention is paid to the drug discovery pathway where recent findings show the beneficial effect of small molecule antagonists of the CGRP receptors for the relief of the migraine attack and of monoclonal antibodies against CGRP or the CGRP receptor for migraine prevention.
Del 256 - Handbook of Experimental Pharmacology
Bile Acids and Their Receptors
AvStefano Fiorucci,Eleonora Distrutti
Inbunden, Engelska, 2019
1 702 kr
Skickas inom 10-15 vardagar
This book focusses on the latest results related to the field of bile acids as signaling molecules and describes how these receptors have become a major pharmacological target. It covers all major areas of research in this field, from genetics, chemistry, in silico modeling, molecular biology to clinical applications, offering a cross-country view of the functional role of bile acids as signaling molecules, virtually acting on all major areas of metabolism. While FXR and GPBAR1 are essential bile acid sensors that integrate the de novo bile acid synthesis with intestinal microbiota and liver metabolism, in a broader sense, BARs play a pathogenic role in the development of common human alignments including liver, intestinal and metabolic disorders, such as steatosis (NAFLD) and steato-hepatitis (NASH), diabetes, obesity and atherosclerosis.
Del 256 - Handbook of Experimental Pharmacology
Bile Acids and Their Receptors
AvStefano Fiorucci,Eleonora Distrutti
Häftad, Engelska, 2020
1 250 kr
Skickas inom 10-15 vardagar
This book focusses on the latest results related to the field of bile acids as signaling molecules and describes how these receptors have become a major pharmacological target. It covers all major areas of research in this field, from genetics, chemistry, in silico modeling, molecular biology to clinical applications, offering a cross-country view of the functional role of bile acids as signaling molecules, virtually acting on all major areas of metabolism. While FXR and GPBAR1 are essential bile acid sensors that integrate the de novo bile acid synthesis with intestinal microbiota and liver metabolism, in a broader sense, BARs play a pathogenic role in the development of common human alignments including liver, intestinal and metabolic disorders, such as steatosis (NAFLD) and steato-hepatitis (NASH), diabetes, obesity and atherosclerosis.
Del 257 - Handbook of Experimental Pharmacology
Good Research Practice in Non-Clinical Pharmacology and Biomedicine
AvAnton Bespalov,Martin C. Michelm. fl.
Inbunden, Engelska, 2020
572 kr
Skickas inom 10-15 vardagar
This open access book, published under a CC BY 4.0 license in the Pubmed indexed book series Handbook of Experimental Pharmacology, provides up-to-date information on best practice to improve experimental design and quality of research in non-clinical pharmacology and biomedicine.
Del 257 - Handbook of Experimental Pharmacology
Good Research Practice in Non-Clinical Pharmacology and Biomedicine
AvAnton Bespalov,Martin C. Michelm. fl.
Häftad, Engelska, 2020
572 kr
Skickas inom 10-15 vardagar
This open access book, published under a CC BY 4.0 license in the Pubmed indexed book series Handbook of Experimental Pharmacology, provides up-to-date information on best practice to improve experimental design and quality of research in non-clinical pharmacology and biomedicine.
Del 259 - Handbook of Experimental Pharmacology
Lipid Signaling in Human Diseases
AvJulian Gomez-Cambronero,Michael A. Frohman
Inbunden, Engelska, 2020
1 702 kr
Skickas inom 10-15 vardagar
Lipids are an integral part of cell membrane architecture, are intermediaries in cell metabolism, and are involved in transmitting cell signals from hormones, growth factors and nutrients. A number of lipases and phospholipases, lipid kinases, lipid phosphatases, sphingosine kinases, and their reaction products have been implicated in fundamental cellular processes including cell proliferation, division and migration. These enzymes and their products underlie the molecular mechanisms of numerous human diseases, in particular metabolic disease (diabetes), cancer, neurodegenerative disease and cardiovascular disease.Over the last decade, studies have advanced to the point that a number of inhibitors for these enzymes have been developed to attempt to ameliorate these conditions; some of the inhibitors are currently in human clinical trial. The need for this book is to review the current status of this field and the prospect for the inhibitors to be clinically important.
Del 259 - Handbook of Experimental Pharmacology
Lipid Signaling in Human Diseases
AvJulian Gomez-Cambronero,Michael A. Frohman
Häftad, Engelska, 2021
1 702 kr
Skickas inom 10-15 vardagar
Lipids are an integral part of cell membrane architecture, are intermediaries in cell metabolism, and are involved in transmitting cell signals from hormones, growth factors and nutrients. A number of lipases and phospholipases, lipid kinases, lipid phosphatases, sphingosine kinases, and their reaction products have been implicated in fundamental cellular processes including cell proliferation, division and migration. These enzymes and their products underlie the molecular mechanisms of numerous human diseases, in particular metabolic disease (diabetes), cancer, neurodegenerative disease and cardiovascular disease.Over the last decade, studies have advanced to the point that a number of inhibitors for these enzymes have been developed to attempt to ameliorate these conditions; some of the inhibitors are currently in human clinical trial. The need for this book is to review the current status of this field and the prospect for the inhibitors to be clinically important.
Del 258 - Handbook of Experimental Pharmacology
Substance Use Disorders
From Etiology to Treatment
AvMichael A. Nader,Yasmin L. Hurd
Inbunden, Engelska, 2020
1 702 kr
Skickas inom 10-15 vardagar
The purpose of this book is to provide a broad scope of substance use disorder research and how these findings can impact treatment outcomes. The research and outcomes described in this book represent important principles related to identifying and understanding factors related to substance use disorders. The first section is dedicated to methodology including population-based surveys, basic neuroanatomy, chemistry, molecular biology, behavioral models and brain imaging. The second section utilizes this methodology in research related to opioids, cocaine, marijuana, alcohol and nicotine. The book is aimed at both professionals (academics, clinicians, practitioners) and students or trainees.
Del 258 - Handbook of Experimental Pharmacology
Substance Use Disorders
From Etiology to Treatment
AvMichael A. Nader,Yasmin L. Hurd
Häftad, Engelska, 2021
1 702 kr
Skickas inom 10-15 vardagar
The purpose of this book is to provide a broad scope of substance use disorder research and how these findings can impact treatment outcomes. The research and outcomes described in this book represent important principles related to identifying and understanding factors related to substance use disorders. The first section is dedicated to methodology including population-based surveys, basic neuroanatomy, chemistry, molecular biology, behavioral models and brain imaging. The second section utilizes this methodology in research related to opioids, cocaine, marijuana, alcohol and nicotine. The book is aimed at both professionals (academics, clinicians, practitioners) and students or trainees.
Del 260 - Handbook of Experimental Pharmacology
Concepts and Principles of Pharmacology
100 Years of the Handbook of Experimental Pharmacology
AvJames E. Barrett,Clive P. Pagem. fl.
Inbunden, Engelska, 2020
1 928 kr
Skickas inom 10-15 vardagar
Celebrating 100 years of HEP, this volume will discuss key pharmacological discoveries and concepts of the past 100 years. These discoveries have dramatically changed the medical treatment paradigms of many diseases and these concepts have and will continue to shape discovery of new medicinies. Newly evolving technologies will similarly be discussed as they will shape the future of the pharmacology and, accordingly, medical therapy.
Pediatric Pharmacotherapy
AvWieland Kiess,Matthias Schwabm. fl.
Inbunden, Engelska, 2020
1 702 kr
Skickas inom 10-15 vardagar
This volume provides readers with the most updated scientific information on the efficacy and safety of medicines for children and adolescents. The book enriches the understanding of pediatric pharmacotherapy for health professionals, regulatory agencies, pharmaceutical companies and learned societies. It contains important information on the pharmacodynamics and pharmacokinetics of drugs. It summarizes the latest investigations on the effects of pharmacological treatments in relation to and dependent on age, gender, fat mass and disease status. Therefore and importantly, this volume reviews the latest data on how pharmacotherapy has to be adjusted and personalized in regards to stages of development and during the pediatric lifespan from neonate through adolescence. In addition, the topic of rare diseases and special challenges for pharmacotherapy will be included and will provide readers with the necessary knowledge to handle complex diseases and treatment strategies especially in relation to pharmacotherapy of rare and orphan diseases.
Del 261 - Handbook of Experimental Pharmacology
Pediatric Pharmacotherapy
AvWieland Kiess,Matthias Schwabm. fl.
Häftad, Engelska, 2021
1 702 kr
Skickas inom 10-15 vardagar
This volume provides readers with the most updated scientific information on the efficacy and safety of medicines for children and adolescents. The book enriches the understanding of pediatric pharmacotherapy for health professionals, regulatory agencies, pharmaceutical companies and learned societies. It contains important information on the pharmacodynamics and pharmacokinetics of drugs. It summarizes the latest investigations on the effects of pharmacological treatments in relation to and dependent on age, gender, fat mass and disease status. Therefore and importantly, this volume reviews the latest data on how pharmacotherapy has to be adjusted and personalized in regards to stages of development and during the pediatric lifespan from neonate through adolescence. In addition, the topic of rare diseases and special challenges for pharmacotherapy will be included and will provide readers with the necessary knowledge to handle complex diseases and treatment strategies especially in relation to pharmacotherapy of rare and orphan diseases.
Del 262 - Handbook of Experimental Pharmacology
Bone Regulators and Osteoporosis Therapy
AvPaula H. Stern
Inbunden, Engelska, 2020
1 702 kr
Skickas inom 10-15 vardagar
This volume is designed to provide an understanding of current and potential therapies for osteoporosis. The opening chapter introduces the cells of bone and their interactions. Several following chapters describe factors affecting bone including systemic hormones with significant effects on bone, and local mediators including growth factors, prostaglandins, cytokines and chemokines. Topics that have commanded particular attention recently are calcium, FGF-23, nervous system bone interactions. Drugs that cause bone loss provide important information on mechanism as well as therapeutic considerations. An overview of the genetics of bone disorders and a discussion of the pathophysiology of osteoporosis establish the clinical context. The final chapters discuss current and potential osteoporosis treatments.
Del 262 - Handbook of Experimental Pharmacology
Bone Regulators and Osteoporosis Therapy
AvPaula H. Stern
Häftad, Engelska, 2021
1 702 kr
Skickas inom 10-15 vardagar
This volume is designed to provide an understanding of current and potential therapies for osteoporosis. The opening chapter introduces the cells of bone and their interactions. Several following chapters describe factors affecting bone including systemic hormones with significant effects on bone, and local mediators including growth factors, prostaglandins, cytokines and chemokines. Topics that have commanded particular attention recently are calcium, FGF-23, nervous system bone interactions. Drugs that cause bone loss provide important information on mechanism as well as therapeutic considerations. An overview of the genetics of bone disorders and a discussion of the pathophysiology of osteoporosis establish the clinical context. The final chapters discuss current and potential osteoporosis treatments.
Del 263 - Handbook of Experimental Pharmacology
Botulinum Toxin Therapy
AvScott M. Whitcup,Mark Hallett
Inbunden, Engelska, 2021
1 702 kr
Skickas inom 10-15 vardagar
In a rapidly progressing field, Botulinum Toxin Therapy provides both clinicians and basic researchers with the latest science on the structure and function of botulinum toxins and the use of these toxins to treat a wide variety of diseases. Part 1 of the book reviews the basic science of botulinum toxins including advances in our understanding of the molecular structure and mechanism of action of botulinum toxins. This section also discusses the manufacturing and formulation of botulinum toxins for clinical use and the development of novel therapeutic toxins for the future. Part 2 reviews the use of botulinum toxins in clinical practice. It discusses the clinical pharmacology of botulinum toxin drugs and their use in a wide variety of clinical conditions including headache, spasticity, pain, disorders of the genitourinary and gastrointestinal tract, strabismus, and medical aesthetics.
Del 263 - Handbook of Experimental Pharmacology
Botulinum Toxin Therapy
AvScott M. Whitcup,Mark Hallett
Häftad, Engelska, 2022
1 702 kr
Skickas inom 10-15 vardagar
In a rapidly progressing field, Botulinum Toxin Therapy provides both clinicians and basic researchers with the latest science on the structure and function of botulinum toxins and the use of these toxins to treat a wide variety of diseases. Part 1 of the book reviews the basic science of botulinum toxins including advances in our understanding of the molecular structure and mechanism of action of botulinum toxins. This section also discusses the manufacturing and formulation of botulinum toxins for clinical use and the development of novel therapeutic toxins for the future. Part 2 reviews the use of botulinum toxins in clinical practice. It discusses the clinical pharmacology of botulinum toxin drugs and their use in a wide variety of clinical conditions including headache, spasticity, pain, disorders of the genitourinary and gastrointestinal tract, strabismus, and medical aesthetics.
Del 264 - Handbook of Experimental Pharmacology
Reactive Oxygen Species
Network Pharmacology and Therapeutic Applications
AvHarald H. H. W. Schmidt,Pietro Ghezzim. fl.
Inbunden, Engelska, 2021
2 267 kr
Skickas inom 10-15 vardagar
Reactive oxygen species (ROS) have been implicated in almost every human disease phenotype, without much, if any, therapeutic consequence foremost exemplified by the failure of the so-called anti-oxidants. This book is a game changer for the field and many clinical areas such as cardiology and neurology. The term ‘oxidative stress’ is abandoned and replaced with a systems medicine and network pharmacology-based mechanistic approach to disease. The ROS-related drugs discussed here target either ROS- forming or ROS -modifying enzymes for which there is strong clinical evidence. In addition, ROS targets are included as they jointly participate in causal mechanisms of disease. This approach is transforming the ROS field and represents a breakthrough in redox medicine indicating a path to patient benefit. In the coming years more targets and drugs may be discovered, but the approach will remain the same and this book will thus become, and for many years remain, the leadingreference for ROSopathies and their treatment by network pharmacology. Chapter "Soluble Guanylate Cyclase Stimulators and Activators" is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.
Del 264 - Handbook of Experimental Pharmacology
Reactive Oxygen Species
Network Pharmacology and Therapeutic Applications
AvHarald H. H. W. Schmidt,Pietro Ghezzim. fl.
Häftad, Engelska, 2022
2 267 kr
Skickas inom 10-15 vardagar
Reactive oxygen species (ROS) have been implicated in almost every human disease phenotype, without much, if any, therapeutic consequence foremost exemplified by the failure of the so-called anti-oxidants. This book is a game changer for the field and many clinical areas such as cardiology and neurology. The term ‘oxidative stress’ is abandoned and replaced with a systems medicine and network pharmacology-based mechanistic approach to disease. The ROS-related drugs discussed here target either ROS- forming or ROS -modifying enzymes for which there is strong clinical evidence. In addition, ROS targets are included as they jointly participate in causal mechanisms of disease. This approach is transforming the ROS field and represents a breakthrough in redox medicine indicating a path to patient benefit. In the coming years more targets and drugs may be discovered, but the approach will remain the same and this book will thus become, and for many years remain, the leadingreference for ROSopathies and their treatment by network pharmacology. Chapter "Soluble Guanylate Cyclase Stimulators and Activators" is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.
Del 265 - Handbook of Experimental Pharmacology
Organotypic Models in Drug Development
AvMonika Schäfer-Korting,Silvya Stuchi Maria-Englerm. fl.
Inbunden, Engelska, 2021
2 267 kr
Skickas inom 10-15 vardagar
This book provides latest findings in organotypic models in drug development and provides the scientific resonance needed in an emerging field of research in disciplines, such as molecular medicine, physiology, and pathophysiology. Today the research on human-based test systems has gained major interest and funding in the EU and the US has increased over the last years. Moreover, so-called 3R (reduce, replace, refine animal experiments) centres have been established worldwide.
Del 265 - Handbook of Experimental Pharmacology
Organotypic Models in Drug Development
AvMonika Schäfer-Korting,Silvya Stuchi Maria-Englerm. fl.
Häftad, Engelska, 2022
2 267 kr
Skickas inom 10-15 vardagar
This book provides latest findings in organotypic models in drug development and provides the scientific resonance needed in an emerging field of research in disciplines, such as molecular medicine, physiology, and pathophysiology. Today the research on human-based test systems has gained major interest and funding in the EU and the US has increased over the last years. Moreover, so-called 3R (reduce, replace, refine animal experiments) centres have been established worldwide.

Handbook of Experimental Pharmacology – serie

Delta Opioid Receptor Pharmacology and Therapeutic Applications

Voltage-gated Sodium Channels: Structure, Function and Channelopathies

Mechanisms of Drug Resistance in Cancer Therapy

Brown Adipose Tissue

New Psychoactive Substances

Antidepressants

Sleep-Wake Neurobiology and Pharmacology

Nociceptin/Orphanin FQ Peptide Receptor

Nociceptin/Orphanin FQ Peptide Receptor

Calcitonin Gene-Related Peptide (CGRP) Mechanisms

Calcitonin Gene-Related Peptide (CGRP) Mechanisms

Bile Acids and Their Receptors

Bile Acids and Their Receptors

Good Research Practice in Non-Clinical Pharmacology and Biomedicine

Good Research Practice in Non-Clinical Pharmacology and Biomedicine

Lipid Signaling in Human Diseases

Lipid Signaling in Human Diseases

Substance Use Disorders

Substance Use Disorders

Concepts and Principles of Pharmacology

Pediatric Pharmacotherapy

Pediatric Pharmacotherapy

Bone Regulators and Osteoporosis Therapy

Bone Regulators and Osteoporosis Therapy

Botulinum Toxin Therapy

Botulinum Toxin Therapy

Reactive Oxygen Species

Reactive Oxygen Species

Organotypic Models in Drug Development

Organotypic Models in Drug Development