首页 | 官方网站   微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   220篇
  免费   2篇
  国内免费   2篇
医药卫生   224篇
  2023年   1篇
  2022年   5篇
  2021年   10篇
  2020年   5篇
  2019年   6篇
  2018年   10篇
  2017年   2篇
  2016年   6篇
  2015年   6篇
  2014年   12篇
  2013年   11篇
  2012年   11篇
  2011年   18篇
  2010年   6篇
  2009年   8篇
  2008年   11篇
  2007年   3篇
  2006年   9篇
  2005年   6篇
  2004年   5篇
  2003年   4篇
  2002年   7篇
  2001年   9篇
  2000年   8篇
  1999年   12篇
  1998年   6篇
  1997年   4篇
  1996年   3篇
  1995年   1篇
  1994年   2篇
  1992年   1篇
  1991年   1篇
  1988年   2篇
  1987年   1篇
  1986年   2篇
  1985年   1篇
  1984年   2篇
  1982年   1篇
  1980年   1篇
  1975年   1篇
  1974年   1篇
  1970年   1篇
  1968年   1篇
  1938年   1篇
排序方式: 共有224条查询结果,搜索用时 15 毫秒
211.
    
Islatravir (MK‐8591) is a nucleoside analogue in development for the treatment and prevention of HIV‐1. Two phase 1 trials were conducted during initial evaluation of islatravir: rising single doses (Study 1) and rising multiple doses (Study 2) of oral islatravir in male and female participants without HIV (aged 18–60 years). Safety, tolerability, and pharmacokinetics of islatravir (plasma) and islatravir‐triphosphate (peripheral blood mononuclear cells) were assessed. In Study 1, 24 participants, assigned to 1 of 3 panels, received alternating single doses of islatravir in a fasted state from 5 mg to 400 mg, or placebo, over 3 dosing periods; a 30 mg dose was additionally assessed following a high‐fat meal. In Study 2, 8 participants per dose received 3 once‐weekly doses of 10, 30, or 100 mg islatravir or placebo in a fasted state. For each panel in both trials, 6 participants received active drug and 2 received placebo. Islatravir was generally well‐tolerated, with no serious adverse events or discontinuations due to adverse events. Islatravir was rapidly absorbed (median time to maximum plasma concentration 0.5 hours); plasma half‐life was 49–61 h; intracellular islatravir‐triphosphate half‐life was 118–171 h. Plasma exposure increased in an approximately dose‐proportional manner; there was no meaningful food effect. There was a modest degree of intracellular islatravir‐triphosphate accumulation after multiple weekly dosing. After single oral doses of islatravir greater than or equal to 5 mg, intracellular islatravir‐triphosphate levels were comparable to levels associated with efficacy in preclinical studies. These results warrant continued clinical investigation of islatravir.

Study Highlights
  • WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?
​Current HIV treatment and prevention strategies have limitations, and novel agents that offer improved safety and tolerability, a high barrier to HIV resistance, and more convenient dosing regimens are required.
  • WHAT QUESTION DID THIS STUDY ADDRESS?
Two phase 1 studies in participants without HIV assessed safety and pharmacokinetics of rising single and multiple doses of oral islatravir, a nucleoside analogue, to support continued development for the treatment and prevention of HIV‐1 infection.
  • WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?
Islatravir was generally well‐tolerated at single doses up to 400 mg. Oral doses of islatravir greater than or equal to 10 mg resulted in intracellular peripheral blood mononuclear cell levels of the active form, islatravir‐triphosphate, comparable to those associated with antiviral efficacy in preclinical studies.
  • HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?
These studies provide important safety and pharmacokinetic information about islatravir in adults without HIV, which will be used to support further clinical investigation of islatravir for the treatment and prevention of HIV‐1 infection.  相似文献   
212.
213.
This study discusses quality of life in post-socialist Mongolia. Yadargaa, a fatigue-related illness in traditional Mongolian medicine, results from lifestyle imbalance. We examine the distribution of yadargaa and its association to socioeconomic changes under capitalism. Ethnographic interviews concerning yadargaa were conducted with health professionals, yadargaa patients, and laypersons. Epidemiological methods were used to identify risk groups, to estimate the point prevalence, and to assess the distribution of meanings and interpretations of yadargaa. The epidemiological sample included 194 individuals, half urban and half rural. Nearly half of the epidemiological sample suffered from yadargaa (49%). These yadargaa sufferers felt that they benefited less than non-yadargaa subjects from the current socioeconomic changes. Among these, perceived change in employment opportunities was one of the best predictors of yadargaa. Additionally, yadargaa sufferers were predominantly women, the elderly, and urban residents. Yadargaa varies greatly in presentation; Western psychiatric categories are only able to explain half of yadargaa cases. In conclusion, yadargaa strongly associates with disenfranchised groups in the capitalist economy. As a culturally constructed indicator of quality of life, yadargaa is a window into the lives of women and men in post-socialist Mongolia.  相似文献   
214.
Summary Urgent coverage of myocardial defects or even the potential replacement of cardiac muscle as a life-saving maneuver appears to be a theoretical advantage of skeletal muscle flaps. Since the heart commonly becomes exposed in the xiphoid region following median sternotomy, the role of the rectus abdominis muscle at least for transposition as an onlay patch for direct suturing and reinforcement of the myocardium has proven applicability. This option requires that the internal mammary artery has remained patent, thus discretion in its use for coronary artery revascularization should be emphasized.  相似文献   
215.
Tetradenia riparia is one of the most popular medicinal plants in Rwanda. Previously, several new substances have been isolated from the leaves of this plant, including a new diterpene diol, i.e. 8(14),15-sandaracopimaradiene-7 alpha,18-diol. This new diterpene diol exhibits significant antimicrobial activity against several bacteria and fungi. The minimum inhibitory concentration (MIC) of the substance for microorganisms which were inhibited ranged from 6.25 to 100 micrograms/ml.  相似文献   
216.
MR cholangiography: techniques and clinical applications   总被引:9,自引:0,他引:9  
Magnetic resonance cholangiography (MRCP) is a new non-invasive imaging technique for the evaluation of bilio-pancreatic disorders. Different sequences, using both breathhold and non-breathhold techniques, have been employed in order to obtain MRCP images. The authors discuss the technical aspects, particularly focusing their attention on a non-breathhold, three-dimensional, fat-suppressed turbo-spin-echo sequence, optimized on a 0.5-T magnet with 15 mT/m gradients. Clinical applications of MRCP are evaluated, presenting data from both the literature and personal experience. The main indication for MRCP study is represented by the evaluation of common bile duct obstruction, with the aim of assessing the presence of the obstruction (accuracy 85–100 %) and, subsequently, its level (accuracy 91–100 %) and its cause. The utility of associating conventional MR images to MRCP in malignant strictures in order to characterize and stage the malignant lesions is also discussed. Finally, data are presented regarding the indications and utility of MR pancreatography in the evaluation of patients with chronic pancreatitis. Received 24 July 1997; Revision received 30 October 1997; Accepted 16 December 1997  相似文献   
217.
218.
219.

Purpose

Elbasvir (MK-8742) and grazoprevir (MK-5172; Merck & Co, Inc, Kenilworth, New Jersey) are hepatitis C virus (HCV)-specific inhibitors of the nonstructural protein 5A phosphoprotein and the nonstructural protein 3/4A protease, respectively. The aims of these studies were to evaluate the antiviral activity and safety of different doses of elbasvir or grazoprevir each administered as monotherapy to participants infected with either HCV genotype (GT) 1 or GT3.

Methods

These 2 double-blind, randomized, placebo-controlled, sequential-panel, multiple ascending dose studies were conducted to assess the safety and pharmacodynamics of 5 days of once-daily elbasvir or 7 days of once-daily grazoprevir in adult male participants chronically infected with either HCV GT1 or GT3.

Findings

Oral administration of elbasvir or grazoprevir once daily exhibited potent antiviral activity in participants with chronic GT1 or GT3 HCV infections. HCV RNA levels declined rapidly (within 1 day for elbasvir and 2 days for grazoprevir). At 50 mg of elbasvir once daily, the mean maximum reductions in HCV RNA from baseline were 5.21, 4.17, and 3.12 log10 IU/mL for GT1b-, GT1a-, and GT3-infected participants, respectively. At 100 mg of grazoprevir once daily, the mean maximum reductions in HCV RNA from baseline were 4.74 and 2.64 log10 IU/mL for GT1- and GT3-infected participants.

Implications

The results in the elbasvir monotherapy study showed that 10 to 50 mg of elbasvir was associated with a rapid decline in HCV viral load; the results in the grazoprevir monotherapy study suggest that doses of 50 mg of grazoprevir and higher are on the maximum response plateau of the dose–response curve for GT1-infected participants. The results of these proof-of-concept studies provided preliminary data for the selection of the dosages of elbasvir and grazoprevir to test in Phase II and III clinical studies. ClinicalTrials.gov identifiers: NCT00998985 (Protocol 5172-004) and NCT01532973 (Protocol 8742-002).  相似文献   
220.
An overview is provided of the methodologies used in determining the time to steady state for Phase 1 multiple dose studies. These methods include NOSTASOT (no-statistical-significance-of-trend), Helmert contrasts, spline (quadratic) regression, effective half life for accumulation, nonlinear mixed effects modeling, and Bayesian approach using Markov Chain Monte Carlo (MCMC) methods. For each methodology we describe its advantages and disadvantages. The first two methods do not require any distributional assumptions for the pharmacokinetic (PK) parameters and are limited to average assessment of steady state. Also spline regression which provides both average and individual assessment of time to steady state does not require any distributional assumptions for the PK parameters. On the other hand, nonlinear mixed effects modeling and Bayesian hierarchical modeling which allow for the estimation of both population and subject-specific estimates of time to steady state do require distributional assumptions on PK parameters. The current investigation presents eight case studies for which the time to steady state was assessed using the above mentioned methodologies. The time to steady state estimates obtained from nonlinear mixed effects modeling, Bayesian hierarchal approach, effective half life, and spline regression were generally similar.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司    京ICP备09084417号

京公网安备 11010802026262号