首页 | 本学科首页   官方微博 | 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   2324篇
  免费   143篇
  国内免费   9篇
  2023年   28篇
  2022年   32篇
  2021年   114篇
  2020年   50篇
  2019年   69篇
  2018年   107篇
  2017年   67篇
  2016年   78篇
  2015年   119篇
  2014年   131篇
  2013年   172篇
  2012年   164篇
  2011年   171篇
  2010年   77篇
  2009年   83篇
  2008年   102篇
  2007年   85篇
  2006年   99篇
  2005年   72篇
  2004年   54篇
  2003年   60篇
  2002年   40篇
  2001年   40篇
  2000年   41篇
  1999年   33篇
  1998年   15篇
  1997年   11篇
  1994年   23篇
  1993年   11篇
  1992年   19篇
  1991年   23篇
  1990年   25篇
  1989年   22篇
  1988年   14篇
  1987年   21篇
  1986年   18篇
  1985年   24篇
  1984年   17篇
  1983年   15篇
  1982年   9篇
  1981年   9篇
  1979年   8篇
  1977年   11篇
  1975年   7篇
  1974年   10篇
  1973年   8篇
  1972年   8篇
  1971年   8篇
  1970年   7篇
  1966年   6篇
排序方式: 共有2476条查询结果,搜索用时 15 毫秒
1.
Among all the metabolites present in the plasma, lipids, mainly triacylglycerol and diacylglycerol, show extensive circadian rhythms. These lipids are transported in the plasma as part of lipoproteins. Lipoproteins are synthesized primarily in the liver and intestine and their production exhibits circadian rhythmicity. Studies have shown that various proteins involved in lipid absorption and lipoprotein biosynthesis show circadian expression. Further, intestinal epithelial cells express circadian clock genes and these genes might control circadian expression of different proteins involved in intestinal lipid absorption. Intestinal circadian clock genes are synchronized by signals emanating from the suprachiasmatic nuclei that constitute a master clock and from signals coming from other environmental factors, such as food availability. Disruptions in central clock, as happens due to disruptions in the sleep/wake cycle, affect intestinal function. Similarly, irregularities in temporal food intake affect intestinal function. These changes predispose individuals to various metabolic disorders, such as metabolic syndrome, obesity, diabetes, and atherosclerosis. Here, we summarize how circadian rhythms regulate microsomal triglyceride transfer protein, apoAIV, and nocturnin to affect diurnal regulation of lipid absorption.  相似文献   
2.
Glycoprotein Ibα (GpIbα) binding ability of A1 domain of von Willebrand factor (vWF) facilitates platelet adhesion that plays a crucial role in maintaining hemostasis and thrombosis at the site of vascular damage. There are both “loss as well as gain of function” mutations observed in this domain. Naturally occurring “gain of function” mutations leave self-activating impacts on the A1 domain which turns the normal binding to characteristic constitutive binding with GPIbα. These “gain of function” mutations are associated with the von Willebrand disease type 2B. In recent years, studies focused on understanding the mechanism and conformational patterns attached to these phenomena have been conducted, but the conformational pathways leading to such binding patterns are poorly understood as of now. To obtain a microscopic picture of such events for the better understanding of pathways, we used molecular dynamics (MD) simulations along with principal component analysis and normal mode analysis to study the effects of Pro1266Leu (Pro503Leu in structural context) mutation on the structure and function of A1 domain of vWF. MD simulations have provided atomic-level details of intermolecular motions as a function of time to understand the dynamic behavior of A1 domain of vWF. Comparative analysis of the trajectories obtained from MD simulations of both the wild type and Pro503Leu mutant suggesting appreciable conformational changes in the structure of mutant which might provide a basis for assuming the “gain of function” effects of these mutations on the A1 domain of vWF, resulting in the constitutive binding with GpIbα.  相似文献   
3.
4.
Thirty-day-old plants of mustard (Brassica juncea L.) were sprayed with 10−10, 10−8, or 10−6 M aqueous solution of 28-homobrassinolide (HBR). The HBR-treated plants were healthier than those treated with water and yielded more. Maximum increase over control was found in 60-d-old, 10−8 M-HBR-treated plants in fresh and dry mass per plant, carbonic anhydrase (CA, E.C. 4.2.1.1) activity, and net photosynthetic rate (P N), at harvest in number of pods per plant and seed yield per plant (the respective values were 25, 30, 34, 69, 24, and 29 %). A further increase in the concentration of HBR (10−6 M) did not make any additional impact on the growth and yield. Increased CA activity and P N were correlated with growth and seed yield. This revised version was published online in August 2006 with corrections to the Cover Date.  相似文献   
5.
To study lifetimes of certain engineering processes, a lifetime model which can accommodate the nature of such processes is desired. The mixture models of underlying lifetime distributions are intuitively more appropriate and appealing to model the heterogeneous nature of process as compared to simple models. This paper is about studying a 3-component mixture of the Rayleigh distributionsin Bayesian perspective. The censored sampling environment is considered due to its popularity in reliability theory and survival analysis. The expressions for the Bayes estimators and their posterior risks are derived under different scenarios. In case the case that no or little prior information is available, elicitation of hyperparameters is given. To examine, numerically, the performance of the Bayes estimators using non-informative and informative priors under different loss functions, we have simulated their statistical properties for different sample sizes and test termination times. In addition, to highlight the practical significance, an illustrative example based on a real-life engineering data is also given.  相似文献   
6.
7.
There are many peptides known that inhibit the entry of enveloped viruses into cells, including one peptide that is successfully being used in the clinic as a drug. In this review, we discuss the discovery, antiviral activity and mechanism of action of such peptides. While peptide entry inhibitors have been discovered by a wide variety of approaches (structure-based, accidental, intentional, rational and brute force) we show here that they share a common physical chemical property: they are at least somewhat hydrophobic and/or amphipathic and have a propensity to interact with membrane interfaces. We propose that this propensity drives a shared mechanism of action for many peptide entry inhibitors, involving direct interactions with viral and cellular membranes, as well as interactions with the complex hydrophobic protein/lipid interfaces that are exposed, at least transiently, during virus–cell fusion. By interacting simultaneously with the membrane interfaces and other critical hydrophobic surfaces, we hypothesize that peptide entry inhibitors can act by changing the physical chemistry of the membranes, and the fusion protein interfaces bridging them, and by doing so interfere with the fusion of cellular and viral membranes. Based on this idea, we propose that an approach that focuses on the interfacial hydrophobicity of putative entry inhibitors could lead to the efficient discovery of novel, broad-spectrum viral entry inhibitors. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and Kalina Hristova.  相似文献   
8.
9.
Dengue fever is the most prevalent arboviral disease in the tropical and sub-tropical regions of the world. The present report describes molecular detection and serotyping of dengue viruses in acute phase blood samples collected from New Delhi, India. Phylogenetic and molecular clock analysis of dengue virus serotype 1 and 3 strains were also investigated. Dengue virus infection was detected in 68.87% out of 604 samples tested by RT-PCR between 2011 & 2014. Dengue serotype 1 was detected in 25.48% samples, dengue serotype 2 in 79.56% samples and dengue serotype 3 in 11.29% samples. Dengue serotype 4 was not detected. Co-infection by more than one dengue serotype was detected in 18.26% samples. Envelope gene of 29 DENV-1 and 14 DENV-3 strains were sequenced in the study. All the DENV-1 strains grouped with the American African genotype. All DENV-3 strains were found to belong to Genotype III. Nucleotide substitution rates of dengue 1 and 3 viruses were determined in the study. Time to the most recent common ancestor (TMRCA) of dengue 1 viruses was determined to be 132 years. TMRCA of DENV-3 viruses was estimated to be 149 years. Bayesian skyline plots were constructed for Indian DENV-1 and 3 strains which showed a decrease in population size since 2005 in case of DENV- 1 strains while no change was observed in recent years in case of DENV-3 strains. The study also revealed a change in the dominating serotype in Delhi, India in recent years. The study will be helpful in formulating control strategies for the outbreaks. In addition, it will also assist in tracking the movement and evolution of this emerging virus.  相似文献   
10.
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