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   4961篇
  免费   442篇
  2023年   47篇
  2022年   37篇
  2021年   154篇
  2020年   121篇
  2019年   138篇
  2018年   165篇
  2017年   140篇
  2016年   246篇
  2015年   307篇
  2014年   325篇
  2013年   376篇
  2012年   452篇
  2011年   429篇
  2010年   278篇
  2009年   242篇
  2008年   296篇
  2007年   273篇
  2006年   248篇
  2005年   230篇
  2004年   179篇
  2003年   176篇
  2002年   161篇
  2001年   46篇
  2000年   35篇
  1999年   36篇
  1998年   39篇
  1997年   24篇
  1996年   25篇
  1995年   18篇
  1994年   21篇
  1993年   16篇
  1992年   8篇
  1991年   19篇
  1990年   5篇
  1989年   11篇
  1988年   6篇
  1987年   7篇
  1986年   4篇
  1985年   4篇
  1984年   6篇
  1983年   8篇
  1982年   5篇
  1981年   5篇
  1977年   4篇
  1976年   7篇
  1975年   2篇
  1973年   2篇
  1972年   3篇
  1971年   2篇
  1968年   2篇
排序方式: 共有5403条查询结果,搜索用时 15 毫秒
1.
2.
The melanocortin system includes five G-protein coupled receptors (family A) defined as MC1R-MC5R, which are stimulated by endogenous agonists derived from proopiomelanocortin (POMC). The melanocortin system has been intensely studied for its central actions in body weight and energy expenditure regulation, which are mainly mediated by MC4R. The pituitary gland is the source of various POMC-derived hormones released to the circulation, which raises the possibility that there may be actions of the melanocortins on peripheral energy homeostasis. In this study, we examined the molecular signaling pathway involved in α-MSH-stimulated glucose uptake in differentiated L6 myotubes and mouse muscle explants. In order to examine the involvement of AMPK, we investigate α-MSH stimulation in both wild type and AMPK deficient mice. We found that α-MSH significantly induces phosphorylation of TBC1 domain (TBC1D) family member 1 (S237 and T596), which is independent of upstream PKA and AMPK. We find no evidence to support that α-MSH-stimulated glucose uptake involves TBC1D4 phosphorylation (T642 and S704) or GLUT4 translocation.  相似文献   
3.
Abstract .The effect of the introduction of the entomophagous copepod Mesocyclops longisetus (Acuacultura F.C.B. strain) on the survival of Aedes aegypti immature stages in car tyres was evaluated under semi-natural conditions in the municipality of Merida, Yucatan, Mexico. Life tables were constructed for the immature stages of the mosquito in the presence and absence of M. longisetus , and the survival data were compared using log–linear models. The data set was adjusted using the GLIM statistical package and the quality of adjustment was evaluated with a chi-squared test . Survivorship curves were constructed for each treatment.
In the absence of M. longisetus , the survivorship of Ae. aegypti immature stages averaged 9%. The highest mortality rate was observed during the fourth larval instar (54%) and the resulting survival pattern corresponded to a type II survivorship curve. The mortality rate of Ae. aegypti first-instar larvae (fifty per tyre) increased more than 200-fold in the presence of M. longisetus (twenty per tyre) and the highest mortality was during the first two larval instars, where it reached 98.9%, with a resulting survivorship of 0.2%. Overall mortality was sixfold greater in the presence of the copepod than in its absence. The survival pattern of immature stages of Ae. aegypti in the presence of the copepod corresponded to a type III survivorship curve. As M. longisetus was so effective against Ae. aegypti immature stages in tyres under semi-natural conditions, its long-term effectiveness should be evaluated under socially and ecologically realistic field conditions in Mexico.  相似文献   
4.
Despite similarities of cellular membranes in all eukaryotes, every compartment displays characteristic and often unique features which are important for the functions of the specific organelles. In the present study, we biochemically characterized the plasma membrane of the methylotrophic yeast Pichia pastoris with emphasis on the lipids which form the matrix of this compartment. Prerequisite for this effort was the design of a standardized and reliable isolation protocol of the plasma membrane at high purity. Analysis of isolated plasma membrane samples from P. pastoris revealed an increase of phosphatidylserine and a decrease of phosphatidylcholine compared to bulk membranes. The amount of saturated fatty acids in the plasma membrane was higher than in total cell extracts. Ergosterol, the final product of the yeast sterol biosynthetic pathway, was found to be enriched in plasma membrane fractions, although markedly lower than in Saccharomyces cerevisiae. A further characteristic feature of the plasma membrane from P. pastoris was the enrichment of inositol phosphorylceramides over neutral sphingolipids, which accumulated in internal membranes. The detailed analysis of the P. pastoris plasma membrane is discussed in the light of cell biological features of this microorganism especially as a microbial cell factory for heterologous protein production.  相似文献   
5.
Biomechanics and Modeling in Mechanobiology - The goal of this work is to assess the impact of vascular anatomy definition degree in the predictions of blood flow models of the arterial network. To...  相似文献   
6.
South America has been influenced by different geoclimatic events ever since its separation from Africa. The inland water fauna has evolved in response to the changing landscape. Currently, there are indications of variations in populations, occurring to different degrees that would indicate a clinal pattern in morphology. Among South America's fauna, the freshwater anomuran, Aegla, is an enigmatic group as a result of its endemicity and is composed of only one genus. Of all the species in this family, Aegla uruguayana has the broadest distribution. Its native habitats have been influenced by several marine transgressions during the Miocene–Quaternary Periods; thus, it is likely that their current distribution has been more recent. Its habitat spreads across a number of isolated basins and sub‐basins that display distinct degrees of isolation/connection, making clinal variation patterns in the morphology of this species possible. The present study aimed to evaluate the pattern of carapace shape variation in A. uruguayana and how it relates to the isolation and/or connection of populations from different basins and sub‐basins, allowing the determination of any extant clinal patterns. The specimens studied belong to 25 separate populations, representing all areas in which the species currently exists. A total of 523 crabs were analyzed. We identified 13 landmarks and four semi‐landmarks in the carapace. The aeglids were divided into seven size intervals to avoid an allometry effect. In each size category, shape relationships analyzed by principal component analysis suggest a geographical pattern corresponding to the distribution of the populations studied. An evaluation of covariation between body shape and geographical coordinates reveals a strong pattern and shows that population distribution had a significant effect on species morphology. Additionally, according to covariance analysis, the variation in shape was not associated with the environmental variables studied. We observed a clinal pattern throughout the species distribution, which could be attributed to genetic drift. It is possible that this process is being amplified by the geographical isolation of the basins, differences in environmental characteristics, and low dispersal ability. © 2014 The Linnean Society of London, Biological Journal of the Linnean Society, 2014, 113 , 914–930.  相似文献   
7.
A mesoscale model of DNA is presented (3SPN.1), extending the scheme previously developed by our group. Each nucleotide is mapped onto three interaction sites. Solvent is accounted for implicitly through a medium-effective dielectric constant and electrostatic interactions are treated at the level of Debye-Hückel theory. The force field includes a weak, solvent-induced attraction, which helps mediate the renaturation of DNA. Model parameterization is accomplished through replica exchange molecular dynamics simulations of short oligonucleotide sequences over a range of composition and chain length. The model describes the melting temperature of DNA as a function of composition as well as ionic strength, and is consistent with heat capacity profiles from experiments. The dependence of persistence length on ionic strength is also captured by the force field. The proposed model is used to examine the renaturation of DNA. It is found that a typical renaturation event occurs through a nucleation step, whereby an interplay between repulsive electrostatic interactions and colloidal-like attractions allows the system to undergo a series of rearrangements before complete molecular reassociation occurs.  相似文献   
8.

Background  

Event-related potentials (ERPs) may be used as a highly sensitive way of detecting subtle degrees of cognitive dysfunction. On the other hand, impairment of cognitive skills is increasingly recognised as a hallmark of patients suffering from multiple sclerosis (MS). We sought to determine the psychophysiological pattern of information processing among MS patients with the relapsing-remitting form of the disease and low physical disability considered as two subtypes: 'typical relapsing-remitting' (RRMS) and 'benign MS' (BMS). Furthermore, we subjected our data to a cluster analysis to determine whether MS patients and healthy controls could be differentiated in terms of their psychophysiological profile.  相似文献   
9.
The present paper offers data on the effect of certain meteorological parameters on the outbreak of forest fires in Galicia (Spain). In a day-to-day analysis, the values of the stability of the air column and the saturation deficit at the lower levels are related to the number of fires occurring in the following 24 h.  相似文献   
10.
[Acyl CoA]monoacylglycerol acyltransferase 2 (MGAT2) is of interest as a target for therapeutic treatment of diabetes, obesity and other diseases which together constitute the metabolic syndrome. In this Letter we report our discovery and optimisation of a novel series of MGAT2 inhibitors. The development of the SAR of the series and a detailed discussion around some key parameters monitored and addressed during the lead generation phase will be given. The in vivo results from an oral lipid tolerance test (OLTT) using the MGAT2 inhibitor (S)-10, shows a significant reduction (68% inhibition relative to na?ve, p <0.01) in plasma triacylglycerol (TAG) concentration.  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