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   665篇
  免费   71篇
  2022年   5篇
  2021年   12篇
  2020年   5篇
  2019年   9篇
  2018年   12篇
  2017年   10篇
  2016年   18篇
  2015年   15篇
  2014年   14篇
  2013年   35篇
  2012年   37篇
  2011年   39篇
  2010年   30篇
  2009年   19篇
  2008年   33篇
  2007年   33篇
  2006年   27篇
  2005年   29篇
  2004年   32篇
  2003年   27篇
  2002年   22篇
  2001年   16篇
  2000年   21篇
  1999年   14篇
  1998年   10篇
  1996年   6篇
  1995年   8篇
  1994年   5篇
  1993年   4篇
  1992年   7篇
  1991年   18篇
  1990年   11篇
  1989年   18篇
  1988年   9篇
  1987年   7篇
  1986年   7篇
  1985年   7篇
  1982年   5篇
  1981年   3篇
  1979年   3篇
  1976年   3篇
  1974年   3篇
  1973年   3篇
  1971年   3篇
  1970年   3篇
  1967年   4篇
  1966年   4篇
  1947年   3篇
  1938年   3篇
  1920年   3篇
排序方式: 共有736条查询结果,搜索用时 41 毫秒
61.
Numerous physical parameters that influence insect physiologyvary substantially with altitude, including temperature, airdensity, and oxygen partial pressure. Here, we review existingliterature and present new empirical data to better characterizethe high-altitude environment, and then consider how this environmentaffects the physiology and evolution of insects. Using weatherballoon data from fifty-three sites across the globe, we estimatea mean altitudinal temperature lapse rate of 6.0 °C/km.We also present empirically determined lapse rates for PO2 andair density. The temperature decline with elevation may substantiallycompromise insect thermoregulation at high altitude. However,heat-transfer models predict that lower air density at elevationreduces convective heat loss of insects by to a surprisinglylarge degree. This effect combined with behavioral thermoregulationand the availability of buffered microhabitats make the netthermal consequences of high-altitude residence strongly context-specific.The decline in PO2 with elevation may compromise insect developmentand physiology, but its effects are difficult to predict withoutsimultaneously considering temperature and air density. Flyinginsects compensate for low air densities with both short-termresponses, such as increased stroke amplitude (but not wingbeatfrequency), and with long-term developmental and/or evolutionaryincreases in wing size relative to body size. Finally, in contrastto predictions based on Bergmann's Rule, a literature surveyof thirty-six insect species suggests that those living in colder,higher altitudes do not tend to have larger body sizes.  相似文献   
62.
63.
The cytotoxic effects of molybdocene dichloride (Cp(2)MoCl(2)) were investigated in V79 Chinese hamster lung cells using the micronucleus assay. Cp(2)MoCl(2) produced significant genotoxic damage whereby 0.2micronuclei/1000 binucleated cells were induced per muM of Cp(2)MoCl(2). Transmission electron microscopic analysis of thin-sectioned cells treated with Cp(2)MoCl(2) (300microM) showed distinct morphological alterations of the nuclei, condensation of chromatin, and a high incidence of polynucleated cells. Implications for the mechanism of antitumor action of molybdocene dichloride are discussed.  相似文献   
64.
MAB007, an IgG1 monoclonal antibody, is unique because of the presence of a free cysteine residue in the Fab region at position 104 on the heavy chain in the CDR3 region. Mass spectrometric analysis of intact MAB007 showed multiple peaks varying in mass by 120-140 Da that cannot be fully attributed to glycosylation isoforms typically present in IgG molecules. Limited proteolysis of MAB007 with Lys-C led to a single cleavage at the C-terminus of a lysine residue in the hinge region of the heavy chain at position 222, generating free Fab and Fc fragments. Reversed-phase liquid chromatography/mass spectrometry analysis of the Fab and Fc fragments revealed several modifications. The Fab fraction showed cysteinylation of a free cysteine in the CDR3 region resulting in a mass shift of 119 Da. Using limited proteolysis, we also identified modifications resulting in a mass increase of 127 Da in the Fc region, corresponding to C-terminal lysine variants in the heavy chain. Other modifications, such as oxidation (+16 Da) and succinimide formation (-17 Da), were also detected in the Fab fragment. The cysteinylation observed after limited proteolysis was confirmed by peptide mapping coupled with tandem mass spectrometry analysis.  相似文献   
65.
Responses of halophytes to high salinities and low water potentials   总被引:3,自引:2,他引:3       下载免费PDF全文
Agrobacterium tumefaciens can induce tumors on thin slices which are excised from Jerusalem artichoke (Helianthus tuberosus) tubers and grown in culture on medium containing minerals and a carbon source. A comparative study was made of the kinetics of cell division in slices under three conditions: (a) slices which were untreated and showed only spontaneous (wound-induced) cell divisions; (b) slices treated with indoleacetic acid at several concentrations; and (c) slices treated with virulent or avirulent bacteria. The earliest spontaneous cell divisions were completed (as detected by the appearance of new daughter cell pairs) by about 3 hours. These cells divide only once. In indoleacetic acid-treated tissue, more cells divide, with the first cell pairs being detected slightly earlier than in slices not subjected to the hormone. The number of cells which divide is roughly proportional to auxin concentration. Tissue treated with virulent bacteria showed only the pattern of spontaneous cell division until about 72 hours, after which another burst of cell division commenced and continued indefinitely. The bacteria-induced growths produced the unusual amino acids which are characteristic of crown gall tumors. The percentage of slices with tumors was sharply reduced if certain avirulent A. tumefaciens strains were applied prior to virulent strains.  相似文献   
66.
Insulin stimulates the mobilization of glucose transporter 4 (GLUT4) storage vesicles to the plasma membrane, resulting in an influx of glucose into target tissues such as muscle and fat. We present evidence that CLIP-associating protein 2 (CLASP2), a protein previously unassociated with insulin action, is responsive to insulin stimulation. Using mass spectrometry-based protein identification combined with phosphoantibody immunoprecipitation in L6 myotubes, we detected a 4.8-fold increase of CLASP2 in the anti-phosphoserine immunoprecipitates upon insulin stimulation. Western blotting of CLASP2 immunoprecipitates with the phosphoantibody confirmed the finding that CLASP2 undergoes insulin-stimulated phosphorylation, and a number of novel phosphorylation sites were identified. Confocal imaging of L6 myotubes revealed that CLASP2 colocalizes with GLUT4 at the plasma membrane within areas of insulin-mediated cortical actin remodeling. CLASP2 is responsible for directing the distal end of microtubules to the cell cortex, and it has been shown that GLUT4 travels along microtubule tracks. In support of the concept that CLASP2 plays a role in the trafficking of GLUT4 at the cell periphery, CLASP2 knockdown by siRNA in L6 myotubes interfered with insulin-stimulated GLUT4 localization to the plasma membrane. Furthermore, siRNA mediated knockdown of CLASP2 in 3T3-L1 adipocytes inhibited insulin-stimulated glucose transport. We therefore propose a new model for CLASP2 in insulin action, where CLASP2 directs the delivery of GLUT4 to cell cortex landing zones important for insulin action.  相似文献   
67.
The proprotein convertases (PCs) furin and proprotein convertase 1/3 (PC1) cleave substrates at dibasic residues along the eukaryotic secretory/endocytic pathway. PCs are evolutionarily related to bacterial subtilisin and are synthesized as zymogens. They contain N-terminal propeptides (PRO) that function as dedicated catalysts that facilitate folding and regulate activation of cognate proteases through multiple-ordered cleavages. Previous studies identified a histidine residue (His69) that functions as a pH sensor in the propeptide of furin (PRO(FUR)), which regulates furin activation at pH~6.5 within the trans-Golgi network. Although this residue is conserved in the PC1 propeptide (PRO(PC1)), PC1 nonetheless activates at pH~5.5 within the dense core secretory granules. Here, we analyze the mechanism by which PRO(FUR) regulates furin activation and examine why PRO(FUR) and PRO(PC1) differ in their pH-dependent activation. Sequence analyses establish that while both PRO(FUR) and PRO(PC1) are enriched in histidines when compared with cognate catalytic domains and prokaryotic orthologs, histidine content in PRO(FUR) is ~2-fold greater than that in PRO(PC1), which may augment its pH sensitivity. Spectroscopy and molecular dynamics establish that histidine protonation significantly unfolds PRO(FUR) when compared to PRO(PC1) to enhance autoproteolysis. We further demonstrate that PRO(FUR) and PRO(PC1) are sufficient to confer organelle sensing on folding and activation of their cognate proteases. Swapping propeptides between furin and PC1 transfers pH-dependent protease activation in a propeptide-dictated manner in vitro and in cells. Since prokaryotes lack organelles and eukaryotic PCs evolved from propeptide-dependent, not propeptide-independent prokaryotic subtilases, our results suggest that histidine enrichment may have enabled propeptides to evolve to exploit pH gradients to activate within specific organelles.  相似文献   
68.
69.
Female phlebotomine sand flies Lutzomyia longipalpis naturally harbor populations of the medically important Leishmania infantum (syn. Leishmania chagasi) parasite in the gut, but the extent to which the parasite interacts with the immune system of the insect vector is unknown. To investigate the sand fly immune response and its interaction with the Leishmania parasite, we identified a homologue for caspar, a negative regulator of immune deficiency signaling pathway. We found that feeding antibiotics to adult female L. longipalpis resulted in an up-regulation of caspar expression relative to controls. caspar was differentially expressed when females were fed on gram-negative and gram-positive bacterial species. caspar expression was significantly down-regulated in females between 3 and 6 days after a blood feed containing Leishmania mexicana amastigotes. RNA interference was used to deplete caspar expression in female L. longipalpis, which were subsequently fed with Leishmania in a blood meal. Sand fly gut populations of both L. mexicana and L. infantum were significantly reduced in caspar-depleted females. The prevalence of L. infantum infection in the females fell from 85 to 45%. Our results provide the first insight into the operation of immune homeostasis in phlebotomine sand flies during the growth of bacterial and Leishmania populations in the digestive tract. We have demonstrated that the activation of the sand fly immune system, via depletion of a single gene, can lead to the abortion of Leishmania development and the disruption of transmission by the phlebotomine sand fly.  相似文献   
70.
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