全文获取类型
收费全文 | 763篇 |
免费 | 53篇 |
出版年
2024年 | 4篇 |
2023年 | 4篇 |
2022年 | 9篇 |
2021年 | 11篇 |
2020年 | 9篇 |
2019年 | 6篇 |
2018年 | 8篇 |
2017年 | 8篇 |
2016年 | 18篇 |
2015年 | 48篇 |
2014年 | 38篇 |
2013年 | 43篇 |
2012年 | 63篇 |
2011年 | 54篇 |
2010年 | 40篇 |
2009年 | 43篇 |
2008年 | 64篇 |
2007年 | 58篇 |
2006年 | 44篇 |
2005年 | 40篇 |
2004年 | 40篇 |
2003年 | 42篇 |
2002年 | 31篇 |
2001年 | 15篇 |
2000年 | 9篇 |
1999年 | 8篇 |
1998年 | 9篇 |
1997年 | 8篇 |
1996年 | 4篇 |
1995年 | 7篇 |
1994年 | 2篇 |
1993年 | 5篇 |
1992年 | 4篇 |
1991年 | 1篇 |
1990年 | 2篇 |
1988年 | 4篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 1篇 |
1978年 | 1篇 |
1976年 | 2篇 |
1972年 | 1篇 |
1970年 | 1篇 |
1969年 | 1篇 |
排序方式: 共有816条查询结果,搜索用时 15 毫秒
721.
722.
Bouffard NA Cutroneo KR Badger GJ White SL Buttolph TR Ehrlich HP Stevens-Tuttle D Langevin HM 《Journal of cellular physiology》2008,216(2):389-395
Vascular smooth muscle cells (SMC) may be directly exposed to blood flow after an endothelial-denuding injury. It is not known whether direct exposure of SMC to shear stress reduces SMC turnover and contributes to the low rate of restenosis after most vascular interventions. This study examines if laminar shear stress inhibits SMC proliferation or stimulates apoptosis. Bovine aortic SMC were exposed to arterial magnitudes of laminar shear stress (11 dynes/cm(2)) for up to 24 h and compared to control SMC (0 dynes/cm(2)). SMC density was assessed by cell counting, DNA synthesis by (3)[H]-thymidine incorporation, and apoptosis by TUNEL staining. Akt, caspase, bax, and bcl-2 phosphorylation were assessed by Western blotting; caspase activity was also measured with an in vitro assay. Analysis of variance was used to compare groups. SMC exposed to laminar shear stress had a 38% decrease in cell number (n = 4, P = 0.03), 54% reduction in (3)[H]-thymidine incorporation (n = 3, P = 0.003), and 15-fold increase in TUNEL staining (n = 4, P < 0.0001). Akt phosphorylation was reduced by 67% (n = 3, P < 0.0001), whereas bax/bcl-2 phosphorylation was increased by 1.8-fold (n = 3, P = 0.01). Caspase-3 activity was increased threefold (n = 5, P = 0.03). Pretreatment of cells with ZVAD-fmk or wortmannin resulted in 42% increased cell retention (n = 3, P < 0.01) and a fourfold increase in apoptosis (n = 3, P < 0.04), respectively. Cells transduced with constitutively-active Akt had twofold decreased apoptosis (n = 3, P < 0.002). SMC exposed to laminar shear stress have decreased proliferation and increased apoptosis, mediated by the Akt pathway. These results suggest that augmentation of SMC apoptosis may be an alternative strategy to inhibit restenosis after vascular injury. 相似文献
723.
Litter decomposition and nitrogen mineralization were investigated in subtropical plantation forests in southern China. The CO2 –C release from incubated litter and the forest floor of Acacia mangium, Acacia auriculaeformis, Eucalyptus citriodora, Pinus elliotii and Schima superba stands were used to estimate relative rates of litter decomposition. Decomposition was not positively correlated with litter nitrogen. E. citridora litter decomposed most rapidly and A. mangium litter most slowly, both with and without the addition of exotic nitrogen. Aerobic incubation and intact soil core incubation at 30 °C over a period of 30 days were used to assess nitrogen mineralization of six forest soils. Although there were differences in results obtained using the two methods, patterns between legume and non-legume species were the same regardless of method. All soils had pH values below 4.5, but this did not prevent nitrification. The dominant form of mineral nitrogen was nitrate for legume species and ammonium for non-legume species. The nitrogen mineralization potential was highest for soils in which legumes were growing. 相似文献
724.
Kezar HS Kilpatrick JM Phillips D Kellogg D Zhang J Morris PE 《Nucleosides, nucleotides & nucleic acids》2005,24(10-12):1817-1830
Forodesine HCl is a potent inhibitor of the enzyme purine nucleoside phosphorylase (PNP) and is currently in clinical trials for the treatment of leukemia and lymphoma. Animal models indicated that forodesine HCl would have low oral bioavailability in humans and it was initially developed as an intravenous formulation. We were interested in identifying analogs of forodesine HCl with improved oral bioavailability. The 2'-deoxy analog (BCX-3040) was synthesized and its pharmacokinetic and pharmacodynamic properties compared with forodesine HCl. 相似文献
725.
Rickman L Scott C Hunt DM Hutchinson T Menéndez MC Whalan R Hinds J Colston MJ Green J Buxton RS 《Molecular microbiology》2005,56(5):1274-1286
726.
In higher plants, determinate leaf primordia arise in regular patterns on the flanks of the indeterminate shoot apical meristem (SAM). The acquisition of leaf form is then a gradual process, involving the specification and growth of distinct domains within the three leaf axes. The recessive corkscrew1 (cks1) mutation of maize (Zea mays) disrupts both leaf initiation patterns in the SAM and domain specification within the mediolateral and proximodistal leaf axes. Specifically, cks1 mutant leaves exhibit multiple midribs and leaf sheath tissue differentiates in the blade domain. Such perturbations are a common feature of maize mutants that ectopically accumulate KNOTTED1-like homeobox (KNOX) proteins in leaf tissue. Consistent with this observation, at least two knox genes are ectopically expressed in cks1 mutant leaves. However, ectopic KNOX proteins cannot be detected. We therefore propose that CKS1 primarily functions within the SAM to establish boundaries between meristematic and leaf zones. Loss of gene function disrupts boundary formation, impacts phyllotactic patterns, and leads to aspects of indeterminate growth within leaf primordia. Because these perturbations arise independently of ectopic KNOX activity, the cks1 mutation defines a novel component of the developmental machinery that facilitates leaf-versus-shoot development in maize. 相似文献
727.
Rheumatoid synovial fibroblasts were used as an immunogen to produce monoclonal antibodies selected for their reactivity with stromal cell antigens. Mice were immunised with low passage whole cell preparations and the subsequent hybridomas were screened by immunohistochemistry on rheumatoid synovium and tonsil sections. The aim was to identify those antibodies that recognised antigens that were restricted to stromal cells and were not expressed on CD45 positive leucocytes. A significant number of antibodies detected antigen that identified endothelial cells. These antibodies were further characterised to determine whether the vessels identified by these antibodies were vascular or lymphatic. From five fusions clones were identified with predominant reactivity with: 1) fibroblasts and endothelial cells; or 2) broad stromal elements (fibroblast, endothelium, epithelium, follicular dendritic cells). A fibroblast-specific antibody that did not also identify vessels was not generated. Examples of each reactivity pattern are discussed. 相似文献
728.
p120-catenin (p120) was originally identified as a tyrosine kinase substrate, and subsequently shown to regulate cadherin-mediated cell-cell adhesion. Binding of the p120 Arm domain to E-cadherin appears to be necessary to maintain adequate cadherin levels for strong adhesion. In contrast, the sequence amino-terminal to the Arm domain confers a negative regulatory function that is likely to be modulated by phosphorylation. Several agents that induce rapid changes in cell-cell adhesion, including PDBu, histamine, thrombin, and LPA, result in significant changes in p120 S/T phosphorylation. In some cases, these changes are PKC-dependent, but the relationship among adhesion, PKC activation, and p120 phosphorylation is unclear, in part because the relevant p120 phosphorylation sites are unknown. As a crucial step toward directly identifying the function of these modifications in adhesion, we have used two-dimensional tryptic mapping and site-directed mutagenesis to pinpoint the constitutive and PKC-modulated sites of p120 S/T phosphorylation. Of eight sites that have been identified, two were selectively phosphorylated in vitro by GSK3 beta, but in vivo treatment of cells with GSK3 beta inhibitors did not eliminate these sites. PKC stimulation in vivo induced potent dephosphorylation at S268, and partial dephosphorylation of several additional sites. Surprisingly, PKC also strongly induced phosphorylation at S873. These data directly link PKC activation to specific changes in p120 phosphorylation, and identify the target sites associated with the mechanism of PKC-dependent adhesive changes induced by agents such as histamine and PDBu. 相似文献
729.
Moos T Trinder D Morgan EH 《American journal of physiology. Gastrointestinal and liver physiology》2002,283(3):G687-G694
Divalent metal transporter I (DMT1) is thought to be involved in transport of iron across the apical cell membrane of villus duodenal cells. To determine its role in hereditary hemochromatosis (HH), we used beta2-microglobulin knockout (B2M-/-) mice that accumulate iron as in HH. The B2M-/- and control C57BL/6 (B2M+/+) mice were fed diets with different iron contents. Increasing the iron availability increased plasma iron levels in both B2M+/+ and B2M-/- mice. Reducing the iron availability decreased the plasma iron concentration in B2M+/+ mice but was without effect on plasma iron in B2M-/- mice. DMT1 was not detectable in mice fed normal or iron-loaded diets when using immunohistochemistry. In Western blots, however, the protein was consistently observed regardless of the dietary regimen. DMT1 expression was increased to the same extent in B2M+/+ and B2M-/- mice when fed an iron-poor diet. In both strains of mice fed an iron-poor diet, DMT1 was evenly distributed in the differentiated enterocytes from the base to the tip of the villi but was absent from the crypts of Lieberkühn. These data suggest that the observed effects were due to the state of iron deficiency in mucosal cells rather than genetic defect. 相似文献
730.