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   2985篇
  免费   189篇
  国内免费   9篇
  3183篇
  2023年   59篇
  2022年   77篇
  2021年   128篇
  2020年   67篇
  2019年   82篇
  2018年   106篇
  2017年   96篇
  2016年   125篇
  2015年   178篇
  2014年   164篇
  2013年   238篇
  2012年   244篇
  2011年   249篇
  2010年   144篇
  2009年   127篇
  2008年   145篇
  2007年   142篇
  2006年   123篇
  2005年   94篇
  2004年   87篇
  2003年   69篇
  2002年   75篇
  2001年   28篇
  2000年   31篇
  1999年   39篇
  1998年   17篇
  1997年   18篇
  1996年   10篇
  1995年   18篇
  1994年   17篇
  1993年   8篇
  1992年   10篇
  1991年   9篇
  1990年   9篇
  1989年   14篇
  1988年   11篇
  1987年   12篇
  1986年   7篇
  1985年   10篇
  1984年   12篇
  1983年   8篇
  1982年   6篇
  1981年   9篇
  1980年   4篇
  1979年   7篇
  1978年   5篇
  1976年   7篇
  1975年   9篇
  1974年   6篇
  1973年   8篇
排序方式: 共有3183条查询结果,搜索用时 15 毫秒
11.
The aim of our study was to assess the water quality of the upper Moselle river by using biological indices. Simultaneous physico-chemical surveys were also undertaken from May 1999 to April 2000. Twelve sampling sites were selected in order to provide a wide range of potential pollution. Chemical analysis did not reveal any major problem of pollution. However a lower water quality resulting from domestic pollution was established for some sampling sites. A biological monitoring combining both macroinvertebrates and macrophytes was performed. Biological indices based on plant community structure and macrophyte composition were not pertinent tools, whereas simple indices based on taxonomic richness of particular groups of macroinvertebrates were strongly correlated with several chemical parameters, showing that such simple biological variables should represent powerful indicators of ecosystem degradation.  相似文献   
12.
Host Determinants of Helicobacter pylori Infection and Its Clinical Outcome   总被引:5,自引:0,他引:5  
Greater than one-half of the world's population harbors Helicobacter pylori. The majority of infected individuals, however, remain asymptomatic, with only 10% to 20% developing diseases, including peptic ulcer disease, gastric cancer, and gastric mucosa–associated lymphoid tissue lymphoma. This article reviews host factors that may predispose an individual to both the acquisition of H. pylori infection and subsequent clinical outcome. Individuals with specific blood group antigens and human leukocyte antigen genotypes may be more susceptible to H. pylori infection. Additional factors, such as the age of acquisition, the host immune response, the site of infection, acid secretion, and interactions with nonhost factors (including bacterial virulence factors and environmental influences) may play a role in determining clinical outcome. Further investigation is required to clarify the mechanisms by which these interactions occur and, more critically, to determine their relative importance. This knowledge will enable the identification of individuals at risk of developing clinical disease with H. pylori infection.  相似文献   
13.
14.
Phage therapy may become a complement to antibiotics in the treatment of chronic Pseudomonas aeruginosa infection. To design efficient therapeutic cocktails, the genetic diversity of the species and the spectrum of susceptibility to bacteriophages must be investigated. Bacterial strains showing high levels of phage resistance need to be identified in order to decipher the underlying mechanisms. Here we have selected genetically diverse P. aeruginosa strains from cystic fibrosis patients and tested their susceptibility to a large collection of phages. Based on plaque morphology and restriction profiles, six different phages were purified from “pyophage”, a commercial cocktail directed against five different bacterial species, including P. aeruginosa. Characterization of these phages by electron microscopy and sequencing of genome fragments showed that they belong to 4 different genera. Among 47 P. aeruginosa strains, 13 were not lysed by any of the isolated phages individually or by pyophage. We isolated two new phages that could lyse some of these strains, and their genomes were sequenced. The presence/absence of a CRISPR-Cas system (Clustered Regularly Interspaced Short Palindromic Repeats and Crisper associated genes) was investigated to evaluate the role of the system in phage resistance. Altogether, the results show that some P. aeruginosa strains cannot support the growth of any of the tested phages belonging to 5 different genera, and suggest that the CRISPR-Cas system is not a major defence mechanism against these lytic phages.  相似文献   
15.
Cieplak M  Hoang TX  Robbins MO 《Proteins》2004,56(2):285-297
The effect of temperature on mechanical unfolding of proteins is studied using a Go-like model with a realistic contact map and Lennard-Jones contact interactions. The behavior of the I27 domain of titin and its serial repeats is contrasted to that of simple secondary structures. In all cases, thermal fluctuations accelerate the unraveling process, decreasing the unfolding force nearly linearly at low temperatures. However, differences in bonding geometry lead to different sensitivity to temperature and different changes in the unfolding pattern. Due to its special native-state geometry, titin is much more thermally and elastically stable than the secondary structures. At low temperatures, serial repeats of titin show a parallel unfolding of all domains to an intermediate state, followed by serial unfolding of the domains. At high temperatures, all domains unfold simultaneously, and the unfolding distance decreases monotonically with the contact order, that is, the sequence distance between the amino acids that form the native contact.  相似文献   
16.
Aim Deep‐sea hydrothermal vents have now been reported along all active mid‐ocean ridges and back‐arc basins, but the boundaries of biogeographic entities remain questionable owing to methodological issues. Here we examine biogeographic patterns of the vent fauna along the East Pacific Rise (EPR) and determine the relative roles of regional and local factors on the distribution of biodiversity associated with mussel beds along a poorly explored zone, the southern EPR (SEPR). Location East Pacific Rise. Methods A species list of macrobenthic invertebrates along the EPR was compiled from the literature and supplemented with data recovered during the French research cruise BIOSPEEDO carried out in 2004 along the SEPR. Biogeographic patterns were assessed by combining the identification of morphological species with a molecular barcoding approach. A multivariate regression tree (MRT) analysis was performed to identify any geographic breaks, and an empirical distribution of species richness was compared with predictions provided by a mid‐domain effect model. Macrofaunal community structure associated with mussel beds along the SEPR was analysed in relation to environmental factors using cluster and canonical redundancy analyses. Results Sequencing of the cytochrome c oxidase subunit I gene revealed the occurrence of several cryptic species complexes along the EPR, with the equator separating the southern and northern clades. Furthermore, during the BIOSPEEDO cruise at least 10 still unnamed species were collected between 7°25′ S and 21°33′ S. The shift in community structure identified by MRT analysis was located south of 17°34′ S or south of 13°59′ S, depending on the data used, suggesting that the southern part of the SEPR (17°25′–21°33′ S) constitutes a biogeographic transition zone in the vent fauna along the EPR. At a regional scale, latitude combined with the type of venting was significantly correlated with the community structure associated with mussel beds. Main conclusions Together, the molecular data, in situ observations, and the distribution of species suggest that the high diversity of vent fauna species presently observed between 17°25′ S and 21°33′ S is probably a result of the overlap of several distinct biogeographic provinces. We argue that this area thus constitutes a biogeographic vent fauna transition zone along the EPR.  相似文献   
17.
High–fat (HF) diet-induced obesity and insulin insensitivity are associated with inflammation, particularly in white adipose tissue (WAT). However, insulin insensitivity is apparent within days of HF feeding when gains in adiposity and changes in markers of inflammation are relatively minor. To investigate further the effects of HF diet, C57Bl/6J mice were fed either a low (LF) or HF diet for 3 days to 16 weeks, or fed the HF-diet matched to the caloric intake of the LF diet (PF) for 3 days or 1 week, with the time course of glucose tolerance and inflammatory gene expression measured in liver, muscle and WAT. HF fed mice gained adiposity and liver lipid steadily over 16 weeks, but developed glucose intolerance, assessed by intraperitoneal glucose tolerance tests (IPGTT), in two phases. The first phase, after 3 days, resulted in a 50% increase in area under the curve (AUC) for HF and PF mice, which improved to 30% after 1 week and remained stable until 12 weeks. Between 12 and 16 weeks the difference in AUC increased to 60%, when gene markers of inflammation appeared in WAT and muscle but not in liver. Plasma proteomics were used to reveal an acute phase response at day 3. Data from PF mice reveals that glucose intolerance and the acute phase response are the result of the HF composition of the diet and increased caloric intake respectively. Thus, the initial increase in glucose intolerance due to a HF diet occurs concurrently with an acute phase response but these effects are caused by different properties of the diet. The second increase in glucose intolerance occurs between 12 - 16 weeks of HF diet and is correlated with WAT and muscle inflammation. Between these times glucose tolerance remains stable and markers of inflammation are undetectable.  相似文献   
18.
Recent investigations have showed that the functional thermogenic adipocytes are present in both infants and adult humans. Accumulating evidence suggests that the coexistence of classical and inducible brown (brite) adipocytes in humans at adulthood and these adipocytes function to generate heat from energy resulting in reducing body fat and improving glucose metabolism. Human thermogenic adipocytes can be differentiated in vitro from stem cells, cell lines, or adipose stromal vascular fraction. Pre-activated human brite adipocytes in vitro can maintain their thermogenic function in normal or obese immunodeficient mice; therefore, they improve glucose homeostasis and reduce fat mass in obese animals. These key findings have opened a new door to use in vitro thermogenic adipocytes as a cell therapy to prevent obesity and related disorders. Thus, this paper intends to highlight our knowledge in aspects of in vitro human brite/brown adipocytes for the further studies.  相似文献   
19.
20.
Stimulation of glutamate binding by the dipeptide L-phenylalanyl-L-glutamate (Phe-Glu) was inhibited by the peptidase inhibitor bestatin, suggesting that the stimulation was caused by glutamate liberated from the dipeptide and not by the dipeptide itself. It further suggests that this form of glutamate binding should be reinterpreted as glutamate sequestration and that stimulation of binding both by dipeptides and after preincubation with high concentrations of glutamate is likely to be due to counterflow accumulation. Several other criteria indicate that most of glutamate binding stimulated by chloride represents glutamate sequestration: Binding is reduced when the osmolarity of the incubation medium is increased, when membranes incubated with [3H]glutamate are lysed before filtration, and when membranes are made permeable by transient exposure to saponin. Moreover, dissociation of bound glutamate after a 100-fold dilution of the incubation medium is accelerated about 50 times by the addition of glutamate to the dilution medium. This result would be anomalous if glutamate were bound to a receptor site; it suggests instead that glutamate is transported in and out of membrane vesicles by a transport system that preferentially mediates exchange between internal and external glutamate. Glutamate binding contains a component of glutamate sequestration even when measured in the absence of chloride. Sequestration is adequately abolished only after treating membranes with detergents; even extensive lysis, sonication, and freezing/thawing may be insufficient.  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