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   641篇
  免费   56篇
  2021年   6篇
  2018年   9篇
  2017年   5篇
  2016年   6篇
  2015年   16篇
  2014年   15篇
  2013年   28篇
  2012年   37篇
  2011年   41篇
  2010年   20篇
  2009年   18篇
  2008年   25篇
  2007年   33篇
  2006年   24篇
  2005年   26篇
  2004年   25篇
  2003年   28篇
  2002年   22篇
  2001年   21篇
  2000年   16篇
  1999年   21篇
  1998年   4篇
  1995年   4篇
  1994年   4篇
  1993年   8篇
  1992年   16篇
  1991年   18篇
  1990年   9篇
  1989年   13篇
  1988年   9篇
  1987年   8篇
  1986年   10篇
  1985年   9篇
  1984年   8篇
  1983年   7篇
  1982年   8篇
  1981年   6篇
  1980年   10篇
  1979年   11篇
  1978年   11篇
  1977年   10篇
  1976年   3篇
  1975年   6篇
  1973年   10篇
  1972年   6篇
  1971年   5篇
  1969年   4篇
  1966年   5篇
  1965年   3篇
  1851年   2篇
排序方式: 共有697条查询结果,搜索用时 15 毫秒
1.
2.
Myocardial infarction (MI) is a major condition causing heart failure (HF). After MI, the renin angiotensin system (RAS) and its signalling octapeptide angiotensin II (Ang II) interferes with cardiac injury/repair via the AT1 and AT2 receptors (AT1R, AT2R). Our study aimed at deciphering the mechanisms underlying the link between RAS and cellular components of the immune response relying on a rodent model of HF as well as HF patients. Flow cytometric analyses showed an increase in the expression of CD4+ AT2R+ cells in the rat heart and spleen post‐infarction, but a reduction in the peripheral blood. The latter was also observed in HF patients. The frequency of rat CD4+ AT2R+ T cells in circulating blood, post‐infarcted heart and spleen represented 3.8 ± 0.4%, 23.2 ± 2.7% and 22.6 ± 2.6% of the CD4+ cells. CD4+ AT2R+ T cells within blood CD4+ T cells were reduced from 2.6 ± 0.2% in healthy controls to 1.7 ± 0.4% in patients. Moreover, we characterized CD4+ AT2R+ T cells which expressed regulatory FoxP3, secreted interleukin‐10 and other inflammatory‐related cytokines. Furthermore, intramyocardial injection of MI‐induced splenic CD4+ AT2R+ T cells into recipient rats with MI led to reduced infarct size and improved cardiac performance. We defined CD4+ AT2R+ cells as a T cell subset improving heart function post‐MI corresponding with reduced infarction size in a rat MI‐model. Our results indicate CD4+ AT2R+ cells as a promising population for regenerative therapy, via myocardial transplantation, pharmacological AT2R activation or a combination thereof.  相似文献   
3.
Vaccinia virus, the prototypic poxvirus, efficiently and faithfully replicates its ~200-kb DNA genome within the cytoplasm of infected cells. This intracellular localization dictates that vaccinia virus encodes most, if not all, of its own DNA replication machinery. Included in the repertoire of viral replication proteins is the I3 protein, which binds to single-stranded DNA (ssDNA) with great specificity and stability and has been presumed to be the replicative ssDNA binding protein (SSB). We substantiate here that I3 colocalizes with bromodeoxyuridine (BrdU)-labeled nascent viral genomes and that these genomes accumulate in cytoplasmic factories that are delimited by membranes derived from the endoplasmic reticulum. Moreover, we report on a structure/function analysis of I3 involving the isolation and characterization of 10 clustered charge-to-alanine mutants. These mutants were analyzed for their biochemical properties (self-interaction and DNA binding) and biological competence. Three of the mutant proteins, encoded by the I3 alleles I3-4, -5, and -7, were deficient in self-interaction and unable to support virus viability, strongly suggesting that the multimerization of I3 is biologically significant. Mutant I3-5 was also deficient in DNA binding. Additionally, we demonstrate that small interfering RNA (siRNA)-mediated depletion of I3 causes a significant decrease in the accumulation of progeny genomes and that this reduction diminishes the yield of infectious virus.  相似文献   
4.
A cDNA termed reg was recently isolated by differential screening of a library prepared from regenerating islets isolated from pancreatic remnants of rats subjected to 90% pancreatectomy and nicotinamide treatment. This led to speculation that this gene may be involved in expansion of beta-cell mass. In the current study we have measured reg expression after implantation and resection of a solid insulinoma tumor into rats, maneuvers known, respectively, to reduce and reexpand the volume of beta-cells in the islet. Animals with an implanted insulinoma tumor became profoundly hypoglycemic. Islet beta-cells declined from the normal 75% of total islet volume to less than 30%, in concert with a marked reduction in the reg mRNA level. Removal of the tumor resulted in a sharp increase in beta-cell replication, as measured by [3H]thymidine incorporation and a return to normal beta-cell volume within 4 days of tumor resection. This was associated with a transient induction in reg expression compared to that in tumor-bearing animals, effectively returning the amount of reg mRNA to the levels found in normal animals within 48 h; at later time points after tumor removal (3-7 days) reg expression declined, but then rose toward normal. In situ hybridization analysis localized the initial induction in reg mRNA expression to the exocrine pancreas. Continuous infusion of insulin into normal rats for 4 days, a maneuver that does not significantly reduce beta-cell mass, resulted in dramatically reduced insulin mRNA in islets, but no change in the levels of reg mRNA. We conclude that the diminution in pancreatic beta-cell mass caused by subcutaneous implantation of an insulinoma is associated with reduced reg gene expression and that the increase in beta-cell replication after resection of the tumor is preceded by return of reg gene expression toward normal.  相似文献   
5.
Since its debut in the mid 1970s, electron crystallography has been a valuable alternative in the structure determination of biological macromolecules. Its reliance on single-layered or double-layered two-dimensionally ordered arrays and the ability to obtain structural information from small and disordered crystals make this approach particularly useful for the study of membrane proteins in a lipid bilayer environment. Despite its unique advantages, technological hurdles have kept electron crystallography from reaching its full potential. Addressing the issues, recent initiatives developed high-throughput pipelines for crystallization and screening. Adding progress in automating data collection, image analysis and phase extension methods, electron crystallography is poised to raise its profile and may lead the way in exploring the structural biology of macromolecular complexes.  相似文献   
6.
Feiglin A  Moult J  Lee B  Ofran Y  Unger R 《PloS one》2012,7(6):e39662
The yeast protein-protein interaction network has been shown to have distinct topological features such as a scale free degree distribution and a high level of clustering. Here we analyze an additional feature which is called Neighbor Overlap. This feature reflects the number of shared neighbors between a pair of proteins. We show that Neighbor Overlap is enriched in the yeast protein-protein interaction network compared with control networks carefully designed to match the characteristics of the yeast network in terms of degree distribution and clustering coefficient. Our analysis also reveals that pairs of proteins with high Neighbor Overlap have higher sequence similarity, more similar GO annotations and stronger genetic interactions than pairs with low ones. Finally, we demonstrate that pairs of proteins with redundant functions tend to have high Neighbor Overlap. We suggest that a combination of three mechanisms is the basis for this feature: The abundance of protein complexes, selection for backup of function, and the need to allow functional variation.  相似文献   
7.
The Regal Fritillary butterfly, Speyeria idalia (Drury) (Lepidoptera: Nymphalidae), has been described as a high gene flow species. Supporting this assertion, previous studies in the Great Plains, where it is still relatively widespread, have found evidence of gene flow across hundreds of kilometers. Using mitochondrial and microsatellite loci, we examined the spatial genetic structure of a very isolated Pennsylvania population of these butterflies that occupies three separate meadows located within ten kilometers of each other. We found restricted gene flow and a distinct structure, with each meadow having a unique genetic signature. Our findings indicate that even a species that normally exhibits high gene flow may show fine-scale genetic subdivision in areas where populations have been largely extirpated.Authors contributed equally.  相似文献   
8.
A bacteriophage growing on Escherichia coli K13, K20, and K23 strains carries a glycanase that catalyzes the hydrolytic cleavage of the beta-ketopyranosidic linkages of 3-deoxy-D-manno-2-octulosonic acid (KDO) in the respective capsular polysaccharides. The main cleavage product of the K23 polysaccharide has been identified by 1H- and 13C-n.m.r. spectroscopy as beta beta Ribfl----7 beta KDOp2----3-beta Ribfl----7KDO. Cleavage of polysaccharides containing alpha-pyranosidic, or 5-substituted beta-pyranosidic KDO is not catalyzed by the enzyme.  相似文献   
9.
Literatur     
Ohne Zusammenfassung  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