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   9288篇
  免费   655篇
  国内免费   2篇
  2022年   37篇
  2021年   99篇
  2020年   65篇
  2019年   84篇
  2018年   105篇
  2017年   95篇
  2016年   186篇
  2015年   297篇
  2014年   353篇
  2013年   501篇
  2012年   528篇
  2011年   550篇
  2010年   396篇
  2009年   330篇
  2008年   476篇
  2007年   534篇
  2006年   488篇
  2005年   529篇
  2004年   489篇
  2003年   469篇
  2002年   480篇
  2001年   127篇
  2000年   93篇
  1999年   118篇
  1998年   162篇
  1997年   104篇
  1996年   111篇
  1995年   124篇
  1994年   118篇
  1993年   121篇
  1992年   89篇
  1991年   82篇
  1990年   99篇
  1989年   92篇
  1988年   71篇
  1987年   77篇
  1986年   69篇
  1985年   75篇
  1984年   77篇
  1983年   79篇
  1982年   65篇
  1981年   78篇
  1980年   61篇
  1979年   57篇
  1978年   50篇
  1977年   51篇
  1976年   47篇
  1975年   43篇
  1974年   41篇
  1973年   37篇
排序方式: 共有9945条查询结果,搜索用时 15 毫秒
931.
Model organisms like the mouse are important tools to learn more about gene function in man. Within the last 20 years many mutant mouse lines have been generated by different methods such as ENU mutagenesis, constitutive and conditional knock-out approaches, knock-down, introduction of human genes, and knock-in techniques, thus creating models which mimic human conditions. Due to pleiotropic effects, one gene may have different functions in different organ systems or time points during development. Therefore mutant mouse lines have to be phenotyped comprehensively in a highly standardized manner to enable the detection of phenotypes which might otherwise remain hidden. The German Mouse Clinic (GMC) has been established at the Helmholtz Zentrum München as a phenotyping platform with open access to the scientific community (www.mousclinic.de; [1]). The GMC is a member of the EUMODIC consortium which created the European standard workflow EMPReSSslim for the systemic phenotyping of mouse models (http://www.eumodic.org/ [2]).  相似文献   
932.
The shape and motion of cells can yield significant insights into the internal operation of a cell. We present a simple, yet versatile, framework that provides multiple metrics of cell shape and cell shape dynamics. Analysis of migrating Dictyostelium discoideum cells shows that global and local metrics highlight distinct cellular processes. For example, a global measure of shape shows rhythmic oscillations suggestive of contractions, whereas a local measure of shape shows wave-like dynamics indicative of protrusions. From a local measure of dynamic shape, or boundary motion, we extract the times and locations of protrusions and retractions. We find that protrusions zigzag, while retractions remain roughly stationary along the boundary. We do not observe any temporal relationship between protrusions and retractions. Our analysis framework also provides metrics of the boundary as whole. For example, as the cell speed increases, we find that the cell shape becomes more elongated. We also observe that while extensions and retractions have similar areas, their shapes differ.  相似文献   
933.
934.
Some Borrelia species are the causative agents of tick-borne Lyme disease responsible for different disabilities depending on species and hosts. Borrelia are highly motile bacterial cells, and light microscopy shows that these spirochetes can associate with each other during movement. Using cryo-electron tomography, we observed closely associated Borrelia cells. Some of these showed a single outer membrane surrounding two longitudinally arranged cytoplasmic cylinders. We also observed fusion of two cytoplasmic cylinders and differences in the surface layer density of fused spirochetes. These processes could play a role in the interaction of Borrelia species with the host's immune system.  相似文献   
935.

Background  

Microarray technology has become a widely used tool in the biological sciences. Over the past decade, the number of users has grown exponentially, and with the number of applications and secondary data analyses rapidly increasing, we expect this rate to continue. Various initiatives such as the External RNA Control Consortium (ERCC) and the MicroArray Quality Control (MAQC) project have explored ways to provide standards for the technology. For microarrays to become generally accepted as a reliable technology, statistical methods for assessing quality will be an indispensable component; however, there remains a lack of consensus in both defining and measuring microarray quality.  相似文献   
936.
937.
Stimulation of almost all mammalian cell types leads to the release of cellular ATP and autocrine feedback through a diverse array of purinergic receptors. Depending on the types of purinergic receptors that are involved, autocrine signalling can promote or inhibit cell activation and fine-tune functional responses. Recent work has shown that autocrine signalling is an important checkpoint in immune cell activation and allows immune cells to adjust their functional responses based on the extracellular cues provided by their environment. This Review focuses on the roles of autocrine purinergic signalling in the regulation of both innate and adaptive immune responses and discusses the potential of targeting purinergic receptors for treating immune-mediated disease.  相似文献   
938.
939.
Root hairs are unicellular extensions of specialized epidermis cells. Under limiting conditions, they significantly increase the water and nutrient uptake capacity of plants by enlarging their root surface. Thus far, little is known about the initiation and growth of root hairs in the monocot model species maize. To gain a first insight into the protein composition of these specialized cells, the 2573 most abundant proteins of maize root hairs attached to four-day-old primary roots of the inbred line B73 were identified by combining 1DE with nanoLC-MS/MS in a shotgun proteomic experiment. Among the identified proteins, homologues of 252 proteins have been previously associated with root hair formation and development in other species. Comparison of the root hair reference proteome of the monocot species maize with the previously published root hair proteome of the dicot species soybean revealed conserved, but also unique, protein functions in root hairs of these two major groups of flowering plants.  相似文献   
940.
DNA-dependent protein kinase (DNA-PK) plays a pivotal role in the repair of DNA double-strand breaks (DSB) and is centrally involved in regulating cellular radiosensitivity. Here, we identify DNA-PK as a key therapeutic target for augmenting accelerated senescence in irradiated human cancer cells. We find that BEZ235, a novel inhibitor of DNA-PK and phosphoinositide 3-kinase (PI3K)/mTOR, abrogates radiation-induced DSB repair resulting in cellular radiosensitization and growth delay of irradiated tumor xenografts. Importantly, radiation enhancement by BEZ235 coincides with a prominent p53-dependent accelerated senescence phenotype characterized by positive β-galactosidase staining, G(2)-M cell-cycle arrest, enlarged and flattened cellular morphology, and increased p21 expression and senescence-associated cytokine secretion. Because this senescence response to BEZ235 is accompanied by unrepaired DNA DSBs, we examined whether selective targeting of DNA-PK also induces accelerated senescence in irradiated cells. Significantly, we show that specific pharmacologic inhibition of DNA-PK, but not PI3K or mTORC1, delays DSB repair leading to accelerated senescence after radiation. We additionally show that PRKDC knockdown using siRNA promotes a striking accelerated senescence phenotype in irradiated cells comparable with that of BEZ235. Thus, in the context of radiation treatment, our data indicate that inhibition of DNA-PK is sufficient for the induction of accelerated senescence. These results validate DNA-PK as an important therapeutic target in irradiated cancer cells and establish accelerated senescence as a novel mechanism of radiosensitization induced by DNA-PK blockade.  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