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   11674篇
  免费   1055篇
  国内免费   1164篇
  13893篇
  2024年   44篇
  2023年   196篇
  2022年   409篇
  2021年   674篇
  2020年   474篇
  2019年   556篇
  2018年   523篇
  2017年   398篇
  2016年   524篇
  2015年   766篇
  2014年   921篇
  2013年   918篇
  2012年   1090篇
  2011年   979篇
  2010年   558篇
  2009年   539篇
  2008年   618篇
  2007年   531篇
  2006年   418篇
  2005年   332篇
  2004年   317篇
  2003年   268篇
  2002年   258篇
  2001年   186篇
  2000年   167篇
  1999年   154篇
  1998年   109篇
  1997年   97篇
  1996年   101篇
  1995年   73篇
  1994年   83篇
  1993年   60篇
  1992年   69篇
  1991年   72篇
  1990年   51篇
  1989年   34篇
  1988年   42篇
  1987年   23篇
  1986年   31篇
  1985年   31篇
  1984年   20篇
  1983年   26篇
  1982年   16篇
  1980年   14篇
  1979年   14篇
  1977年   11篇
  1975年   13篇
  1974年   12篇
  1973年   11篇
  1970年   11篇
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
41.
AnxB1,a novel annexin previously isolated from Cysticercus cellulose,shows high thrombi affinity and anticoagulant activity in vivo.In order to investigate the relationship between structure and biological function,a predicted three-dimensional(3D)model of AnxB1 was generated by homology modeling.This model contains four homologous internal-domains and the Cα trace of domain Ⅰ,Ⅱ and IV shows high similarity.Based on the structure characterization,four sequence-deleted mutants were constructed and expressed as GST fusion proteins in E.coli.Two of the mutants,GST-M3 and GST-M4 reserved high anticoagulant activity(p<0.01 vs.GST).Furthermore,compared with the wild type GST-AnxB1,the immunogenicity of GST-M3 and GST-M4 was reduced significantly(p<0.01)and the molecular weight was lowered to 27 kD and 34 kD,respectively.These observations laid a solid foundation for further study on developing new thrombolytic agents with higher efficiency and lower side effect.  相似文献   
42.
Tau protein is present in six different splice forms in the human brain and interacts with microtubules via either 3 or 4 microtubule binding repeats. An increased ratio of 3 repeat to 4 repeat isoforms is associated with neurodegeneration in inherited forms of frontotemporal dementia. Tau over-expression diminishes axonal transport in several systems, but differential effects of 3 repeat and 4 repeat isoforms have not been studied. We examined the effects of tau on mitochondrial transport and found that both 3 repeat and 4 repeat tau change normal mitochondrial distribution within the cell body and reduce mitochondrial localization to axons; 4 repeat tau has a greater effect than 3 repeat tau. Further, we observed that the 3 repeat and 4 repeat tau cause different alterations in retrograde and anterograde transport dynamics with 3 repeat tau having a slightly stronger effect on axon transport dynamics. Our results indicate that tau-induced changes in axonal transport may be an underlying theme in neurodegenerative diseases associated with isoform specific changes in tau's interaction with microtubules.  相似文献   
43.
Functional characterization of a new human Ad4BP/SF-1 variation, G146A   总被引:4,自引:0,他引:4  
Ad4BP/SF-1 plays key roles at all levels of the hypothalamic-pituitary-steroidogenic organ axis and its functional disruption causes endocrine disorders of these organs. However, only three human subjects with Ad4BP/SF-1 mutations have been reported to date, suggesting limited clinical significance as a cause of inborn adrenal or sexual abnormalities. We report the first functional characterization of a new variation found in the hinge region of human Ad4BP/SF-1, G146A. Resulting from a single nucleotide shift (GGG-->GCG), G146A bears slightly diminished transactivation activity evidenced by both adrenal specific cyp11A promoter and ovary specific cyp19 promoter II. The variation does not affect protein expression or stability, exhibiting no dominant negative effect. G146A has a normal interaction pattern with standard co-regulators and subnuclear distribution pattern, and can be considered as a nonsynonymous single nucleotide polymorphism, since it occurs in normals and patients with adrenal diseases. In normal Japanese the allele C frequency is 8%, while in a preliminary population of patients with adrenal diseases it is elevated to 30%; suggesting the G146A variation might be of clinical importance.  相似文献   
44.
在室内砾耕栽培条件下,通过培养液中加入PEG(Polyethylene glycol 分子量为6000)以调节溶液渗透势,设置对照、弱水分胁迫和强水分胁迫3种处理 (培养液渗透势分别为0.02,-0.1,-0.34 MPa), 从1997年开始对臭柏进行长期干旱胁迫模拟实验.2003年测定了臭柏叶片光合色素和光合特性的季节变化.结果表明:对照区气孔导度季节变化在5月和9月份形成了典型的双峰曲线.尽管对照区的气孔导度明显高于其他两个处理,但日光合量却低于弱水分胁迫区.3个处理Chl a/b的比值在11月至翌年3月的低温期内均升高,以强水分胁迫区的增幅最大,其它月份该比值在3个处理之间没有显著的差异.3个处理的叶绿素总量(Chl a+b)在生长季的5~9月份均有不同程度的上升,但其中以强水分胁迫区增幅最小.在11月至翌年3月的低温期,各处理均大幅提高叶黄素总量(V+A+Z)和热耗散色素比例(A+Z)/(V+A+Z) (V:紫黄质、A:单环氧玉米黄质、Z:玉米黄质);在5~7月份的生长高峰期,各处理则明显降低了叶黄素总量和热耗散色素比例.这种趋势在强水分胁迫区表现的更为显著.  相似文献   
45.
为了探讨CO2浓度升高下不同水稻品种荣优398 (RY)和粤杂889(YZ)吸收重金属Cd差异性的原因,利用水培试验研究了不同浓度Cd处理下两种水稻吸收Cd的差异及根形态的变化特征.结果表明:低Cd处理(5、10、20 μmol·L-1)显著增加水稻生物量;当Cd浓度高于50 μmol·L-1时,Cd胁迫效果开始显现,水稻生物量减少.CO2浓度升高显著增加了水稻的生物量,增加了YZ茎Cd含量而降低了RY茎Cd含量.在5~200 μmol·L-1的Cd浓度下,CO2浓度升高增加了YZ活性根在总根长中的比例,降低了RY活性根的比例.CO2浓度升高下不同水稻品种根形态的变化是导致其对Cd吸收差异性的原因之一.  相似文献   
46.
47.
Microsatellites are widely distributed throughout nearly all genomes which have been extensively exploited as powerful genetic markers for diverse applications due to their high polymorphisms. Their length variations are involved in gene regulation and implicated in numerous genetic diseases even in cancers. Although much effort has been devoted in microsatellite database construction, the existing microsatellite databases still had some drawbacks, such as limited number of species, unfriendly export format, missing marker development, lack of compound microsatellites and absence of gene annotation, which seriously restricted researchers to perform downstream analysis. In order to overcome the above limitations, we developed PSMD (Pan‐Species Microsatellite Database, http://big.cdu.edu.cn/psmd/ ) as a web‐based database to facilitate researchers to easily identify microsatellites, exploit reliable molecular markers and compare microsatellite distribution pattern on genome‐wide scale. In current release, PSMD comprises 678,106,741 perfect microsatellites and 43,848,943 compound microsatellites from 18,408 organisms, which covered almost all species with available genomic data. In addition to interactive browse interface, PSMD also offers a flexible filter function for users to quickly gain desired microsatellites from large data sets. PSMD allows users to export GFF3 formatted file and CSV formatted statistical file for downstream analysis. We also implemented an online tool for analysing occurrence of microsatellites with user‐defined parameters. Furthermore, Primer3 was embedded to help users to design high‐quality primers with customizable settings. To our knowledge, PSMD is the most extensive resource which is likely to be adopted by scientists engaged in biological, medical, environmental and agricultural research.  相似文献   
48.
Jatropha curcas L. is an excellent biofuel crop, which displays a high efficiency of carbon absorption, and seed oil of Jatropha can be efficiently processed to produce high-quality biodiesel. Plant phosphoenolpyruvate carboxylases (PEPCs) play important roles not only in initial fixation of atmospheric CO2 in C4 and Crassulacean acid metabolism (CAM) plants, but also in fatty acid biosynthesis in seeds of oil plants by regulating carbon partitioning. Here, we identified JcPEPC1 from J. curcas L. by homology cloning, and alignment analysis of protein sequence revealed JcPEPC1 was a plant C3-type PEPC, and shared high similarity to PEPC of castor oil plant Ricinus communis. We implemented detailed functional characterization of JcPEPC1 by expression analysis and transgenic tobacco. JcPEPC1 gene expressed in the leaves and seeds of J. curcas L., and remarkable increase of expression level was also detected at seed oil-accumulating stages. We overexpressed JcPEPC1 in tobacco, and showed the enzymatic activity of PEPC in transgenic plants was notably higher than wild type. Gas chromatography (GC) analysis elucidated the composition and total content of fatty acids were also altered. This study indicated JcPEPC1 played a fundamental role in fatty acid biosynthesis in Jatropha seeds. Our results proposed enhanced PEPC activity of Jatropha could improve biosynthesis of fatty acid, which implied critical functions in primary metabolism of non-photosynthetic PEPC.  相似文献   
49.
Significant progress on pig genetics and genomics research has been witnessed in recent years due to the integration of advanced molecular biology techniques, bioinformatics and computational biology, and the collaborative efforts of researchers in the swine genomics community. Progress on expanding the linkage map has slowed down, but the efforts have created a higher-resolution physical map integrating the clone map and BAC end sequence. The number of QTL mapped is still growing and most of the updated QTL mapping results are available through PigQTLdb. Additionally, expression studies using high-throughput microarrays and other gene expression techniques have made significant advancements. The number of identified non-coding RNAs is rapidly increasing and their exact regulatory functions are being explored. A publishable draft (build 10) of the swine genome sequence was available for the pig genomics community by the end of December 2010. Build 9 of the porcine genome is currently available with Ensembl annotation; manual annotation is ongoing. These drafts provide useful tools for such endeavors as comparative genomics and SNP scans for fine QTL mapping. A recent community-wide effort to create a 60K porcine SNP chip has greatly facilitated whole-genome association analyses, haplotype block construction and linkage disequilibrium mapping, which can contribute to whole-genome selection. The future 'systems biology' that integrates and optimizes the information from all research levels can enhance the pig community's understanding of the full complexity of the porcine genome. These recent technological advances and where they may lead are reviewed.  相似文献   
50.
Mechanical strain is one of the important epigenetic factors that cause deformation and differentiation of skeletal muscles. This research was designed to investigate how myoblast deformation occurs after cyclic strain loading. Myoblasts were passaged three times and harvested; various cyclic strains (2.5kPa, 5kPa and 10kPa) were then loaded using a pulsatile mechanical system. The adaptive response of the myoblasts was observed at different time points (0.5h, 1h, 6h and 12h) post-loading. At the early stage of cyclic strain loading (<1h), almost no visible morphological changes were observed in the myoblasts. The actin cytoskeleton showed a disordered arrangement and a weak fluorescence expression; there was little expression of talin. At 6h and 12h post-loading, the myoblasts changed their orientation to parallel (in the 2.5kPa and 5kPa groups) or perpendicular (in the 10kPa group) to the direction of strain. Fluorescence expression of both the actin cytoskeleton and talin was significantly increased. The results suggest that cyclic strain has at least two ways to regulate adaptation of myoblasts: (1) by directly affecting actin cytoskeleton at an early stage post-loading to cause depolymerization; and (2) by later chemical signals transmitted from the extracellular side to intracellular side to initiate repolymerization.  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