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   176篇
  免费   0篇
系统科学   2篇
教育与普及   1篇
现状及发展   21篇
研究方法   13篇
综合类   136篇
自然研究   3篇
  2012年   8篇
  2011年   8篇
  2008年   4篇
  2007年   6篇
  2006年   7篇
  2005年   6篇
  2004年   8篇
  2003年   4篇
  2002年   8篇
  2001年   5篇
  2000年   8篇
  1999年   5篇
  1992年   6篇
  1991年   2篇
  1990年   4篇
  1989年   6篇
  1988年   3篇
  1987年   2篇
  1986年   7篇
  1985年   7篇
  1984年   2篇
  1983年   4篇
  1982年   2篇
  1981年   2篇
  1979年   6篇
  1978年   2篇
  1977年   4篇
  1975年   3篇
  1974年   4篇
  1972年   3篇
  1971年   3篇
  1970年   7篇
  1969年   3篇
  1968年   7篇
  1967年   6篇
  1965年   3篇
  1963年   1篇
排序方式: 共有176条查询结果,搜索用时 15 毫秒
11.
Expression of oncogenic Ras in primary human cells activates p53, thereby protecting cells from transformation. We show that in Ras-expressing IMR-90 cells, p53 is phosphorylated at Ser33 and Ser46 by the p38 mitogen-activated protein kinase (MAPK). Activity of p38 MAPK is regulated by the p53-inducible phosphatase PPM1D, creating a potential feedback loop. Expression of oncogenic Ras suppresses PPM1D mRNA induction, leaving p53 phosphorylated at Ser33 and Ser46 and in an active state. Retrovirus-mediated overexpression of PPM1D reduced p53 phosphorylation at these sites, abrogated Ras-induced apoptosis and partially rescued cells from cell-cycle arrest. Inactivation of p38 MAPK (the product of Mapk14) in vivo by gene targeting or by PPM1D overexpression expedited tumor formation after injection of mouse embryo fibroblasts (MEFs) expressing E1A+Ras into nude mice. The gene encoding PPM1D (PPM1D, at 17q22/q23) is amplified in human breast-tumor cell lines and in approximately 11% of primary breast tumors, most of which harbor wildtype p53. These findings suggest that inactivation of the p38 MAPK through PPM1D overexpression resulting from PPM1D amplification contributes to the development of human cancers by suppressing p53 activation.  相似文献   
12.
Nonlinear and quantum atom optics   总被引:2,自引:0,他引:2  
Rolston SL  Phillips WD 《Nature》2002,416(6877):219-224
Coherent matter waves in the form of Bose-Einstein condensates have led to the development of nonlinear and quantum atom optics - the de Broglie wave analogues of nonlinear and quantum optics with light. In nonlinear atom optics, four-wave mixing of matter waves and mixing of combinations of light and matter waves have been observed; such progress culminated in the demonstration of phase-coherent matter-wave amplification. Solitons represent another active area in nonlinear atom optics: these non-dispersing propagating modes of the equation that governs Bose-Einstein condensates have been created experimentally, and observed subsequently to break up into vortices. Quantum atom optics is concerned with the statistical properties and correlations of matter-wave fields. A first step in this area is the measurement of reduced number fluctuations in a Bose-Einstein condensate partitioned into a series of optical potential wells.  相似文献   
13.
YidC mediates membrane protein insertion in bacteria   总被引:13,自引:0,他引:13  
The basic machinery for the translocation of proteins into or across membranes is remarkably conserved from Escherichia coli to humans. In eukaryotes, proteins are inserted into the endoplasmic reticulum using the signal recognition particle (SRP) and the SRP receptor, as well as the integral membrane Sec61 trimeric complex (composed of alpha, beta and gamma subunits). In bacteria, most proteins are inserted by a related pathway that includes the SRP homologue Ffh, the SRP receptor FtsY, and the SecYEG trimeric complex, where Y and E are related to the Sec61 alpha and gamma subunits, respectively. Proteins in bacteria that exhibit no dependence on the Sec translocase were previously thought to insert into the membrane directly without the aid of a protein machinery. Here we show that membrane insertion of two Sec-independent proteins requires YidC. YidC is essential for E. coli viability and homologues are present in mitochondria and chloroplasts. Depletion of YidC also interferes with insertion of Sec-dependent membrane proteins, but it has only a minor effect on the export of secretory proteins. These results provide evidence for an additional component of the translocation machinery that is specialized for the integration of membrane proteins.  相似文献   
14.
The benthic macroinvertebrate fauna of southern Saskatchewan, Canada, has received little attention relative to other regions of western North America. Therefore, little is known of the related aquatic ecosystem health and biogeography of regional aquatic insects. Here we present the results of an aquatic macroinvertebrate survey for the Pipestone Creek watershed in southeastern Saskatchewan. We qualitatively sampled aquatic macroinvertebrates in 5 sites on 4 dates through spring, summer, and fall 2006. Sampling produced 294 taxa of macroinvertebrates including 25 provincial range extensions to the southeast corner of the province. Presence/absence data of taxa grouped the sites into lentic and lotic sites. However, the relative proportions of the taxa varied greatly among sites, with no 2 sites having a community similarity greater than 50%. Functional feeding group analyses separated the sites into collector-dominated and scraper/grazer-dominated sites. However, the taxonomic make-up of the feeding groups varied among sites and also among dates. A modified Hilsenhoff Biotic Index of the site communities indicated that all were influenced by organic pollution. Results of this study suggest that although the watershed is enormously diverse, its biological communities are likely influenced by organic pollution. Further, range expansions of species found here, such as the stonefly Perlesta placida , have implications for invasion pathways and post-glaciation species islands in a prairie landscape.  相似文献   
15.
Cooperative tandem binding of met repressor of Escherichia coli   总被引:10,自引:0,他引:10  
We present biochemical and genetic data to support the hypothesis that the Escherichia coli met repressor, MetJ, binds to synthetic and natural operator sequences in tandem arrays such that repression depends not only on the affinity of the DNA-protein interaction, but also on protein-protein contacts along the tandem array. This represents a novel form of regulatory switch. Furthermore, there seems to be homology between the organization of the met and trp operators.  相似文献   
16.
17.
Integrins not only bind adhesive ligands, they also act as signalling receptors. Both functions allow the integrin alphaIIbbeta3 to mediate platelet aggregation. Platelet agonists activate alphaIIbbeta3 (inside-out signalling) to allow the binding of soluble fibrinogen. Subsequent platelet aggregation leads to outside-in alphaIIbbeta3 signalling, which results in calcium mobilization, tyrosine phosphorylation of numerous proteins including beta3 itself, increased cytoskeletal reorganisation and further activation of alphaIIbbeta3. Thus, outside-in signals enhance aggregation, although the mechanisms and functional consequences of specific signalling events remain unclear. Here we describe a mouse that expresses an alphaIIbbeta3 in which the tyrosines in the integrin cytoplasmic tyrosine motif have been mutated to phenylalanines. These mice are selectively impaired in outside-in alphaIIbbeta3 signalling, with defective aggregation and clot-retraction responses in vitro, and an in vivo bleeding defect which is characterized by a pronounced tendency to rebleed. These data provide evidence for an important role of outside-in signalling in platelet physiology. Furthermore, they identify the integrin cytoplasmic tyrosine motif as a key mediator of beta-integrin signals and a potential target for new therapeutic agents.  相似文献   
18.
C Miller  E Moczydlowski  R Latorre  M Phillips 《Nature》1985,313(6000):316-318
The recent development of techniques for recording currents through single ionic channels has led to the identification of a K+-specific channel that is activated by cytoplasmic Ca2+. The channel has complex properties, being activated by depolarizing voltages and having a voltage-sensitivity that is modulated by cytoplasmic Ca2+ levels. The conduction behaviour of the channel is also unusual, its high ionic selectivity being displayed simultaneously with a very high unitary conductance. Very little is known about the biochemistry of this channel, largely due to the lack of a suitable ligand for use as a biochemical probe for the channel. We describe here a protein inhibitor of single Ca2+-activated K+ channels of mammalian skeletal muscle. This inhibitor, a minor component of the venom of the Israeli scorpion, Leiurus quinquestriatus, reversibly blocks the large Ca2+-activated K+ channel in a simple biomolecular reaction. We have partially purified the active component, a basic protein of relative molecular mass (Mr) approximately 7,000.  相似文献   
19.
S Phillips  R P Novick 《Nature》1979,278(5703):476-478
  相似文献   
20.
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