全文获取类型
收费全文 | 313篇 |
免费 | 20篇 |
出版年
2021年 | 5篇 |
2020年 | 3篇 |
2019年 | 4篇 |
2018年 | 4篇 |
2015年 | 8篇 |
2014年 | 4篇 |
2013年 | 16篇 |
2012年 | 19篇 |
2011年 | 14篇 |
2010年 | 15篇 |
2009年 | 8篇 |
2008年 | 17篇 |
2007年 | 13篇 |
2006年 | 8篇 |
2005年 | 11篇 |
2004年 | 6篇 |
2003年 | 9篇 |
2001年 | 2篇 |
2000年 | 9篇 |
1999年 | 6篇 |
1998年 | 5篇 |
1997年 | 7篇 |
1996年 | 4篇 |
1994年 | 5篇 |
1993年 | 2篇 |
1992年 | 7篇 |
1991年 | 9篇 |
1990年 | 4篇 |
1989年 | 11篇 |
1988年 | 7篇 |
1987年 | 4篇 |
1986年 | 5篇 |
1985年 | 7篇 |
1984年 | 8篇 |
1983年 | 3篇 |
1982年 | 3篇 |
1981年 | 4篇 |
1980年 | 2篇 |
1978年 | 3篇 |
1977年 | 4篇 |
1975年 | 3篇 |
1974年 | 5篇 |
1973年 | 3篇 |
1972年 | 4篇 |
1969年 | 2篇 |
1968年 | 2篇 |
1964年 | 3篇 |
1961年 | 3篇 |
1960年 | 2篇 |
1957年 | 2篇 |
排序方式: 共有333条查询结果,搜索用时 359 毫秒
11.
12.
Lysophosphatidic acid can activate platelets without increasing 32P-labelling of phosphatidic acid 总被引:2,自引:0,他引:2
Stimulation of platelets by thrombin produced a rise in [32P]phosphatidic acid labelling of platelets which was greater in medium without added calcium than in medium with 2.5 mM calcium. A rise in [32P]lysophosphatidic acid was also seen in platelets stimulated by thrombin in the presence of 2.5 mM extracellular calcium, though it was of lesser magnitude (average 35%) than the rise in phosphatidic acid. In platelets resuspended without added calcium no change in [32P]lysophosphatidic acid was seen in response to thrombin. Lysophosphatidic acid can itself induce platelet aggregation. Similarly to the calcium ionophore A23187, lysophosphatidic acid produced minimal change (in medium with no added calcium) to no change (in medium with 2.5 mM external calcium) in [32P]lysophosphatidic acid. The endoperoxide analog U46619 produced changes in 32P-labelling of platelet phosphatidic and lysophosphatidic acid similar to those produced by thrombin but of lesser magnitude. The results of these studies show that the action of lysophosphatidic acid on platelets differs from the action of thrombin, U46619 and platelet-activating factor, which produce a rapid rise in [32P]phosphatidic acid, and suggests that lysophosphatidic acid, like A23187, largely bypasses the initial receptor-coupled breakdown of phosphoinositides leading to formation of diacylglycerols and phosphatidic acid. 相似文献
13.
The present study has investigated the influence of arachidonate, endoperoxide analogs, and the calcium ionophore A23187 on platelet aggregation and on the phosphorylation of platelet proteins. Following stimulation of platelets by these agents a rapid increase in phosphorylation of three proteins was observed which began at the same time as the initial formation of platelet aggregates. These three proteins were the 260,000 dalton actin-binding protein, a 40,000 dalton protein of unknown function, and the 20,000 dalton myosin light chain. When extensive aggregation was reached, the extent of phosphorylation returned toward baseline. Pretreatment of platelets with aspirin completely inhibited both aggregation and protein phosphorylations induced by arachidonate, but had only partial inhibitory effects on endoperoxide analogs or A23187. Since endoperoxide analogs and A23187 may trigger endogenous production of prostaglandin endoperoxides and thromboxane A2, in addition to having a direct effect of their own, it is probable that the partial inhibition seen was due to inhibition of that component of their effect due to this endogenous production, through other effects of aspirin can not be entirely ruled out. Since recent evidence shows that phosphorylation of myosin light chain results from calcium stimulation of a protein kinase in the presence of calmodulin, the results are consistent with mobilization of calcium as the primary role of the arachidonate-endoperoxide-thromboxane pathway. 相似文献
14.
Michael C. Iannuzzi Robert C. Stern Francis S. Collins Catherine Tom Hon Noriko Hidaka Theresa Strong Lisa Becker Mitchell L. Drumm Marga B. White Bernard Gerrard Michael Dean 《American journal of human genetics》1991,48(2):227-231
Cystic fibrosis (CF) is a recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. We have identified in exon 7 two frameshift mutations, one caused by a two-nucleotide insertion and the other caused by a one-nucleotide deletion; these mutations--CF1154insTC and CF1213delT, respectively, are predicted to shift the reading frame of the protein and to introduce UAA(ochre) termination codons at residues 369 and 368. 相似文献
15.
Loss of function of Arabidopsis NADP‐malic enzyme 1 results in enhanced tolerance to aluminum stress
16.
When an γ‐irradiated Dy‐, Tm‐, Sm‐ or Mn‐doped CaSO4 crystal is impulsively deformed, two peaks appear in the ML intensity versus time curve, whereby the first ML peak is found in the deformation region and the second in the post‐deformation region of the crystals. In this study, intensities Im1 and Im2 corresponding to first and second ML peaks, respectively, increased linearly with an impact velocity v0 of the piston used to deform the crystals, and times tm1 and tm2 corresponding to the first and second ML peaks, respectively, decreased with impact velocity. Total ML intensity initially increased with impact velocity and then reached a saturation value for higher values of impact velocity. ML intensity increased with increasing γ‐doses and size of crystals. Results showed that the electric field produced as a result of charging of newly‐created surfaces caused tunneling of electrons to the valence band of the hole‐trapping centres. The free holes generated moved in the valence band and their subsequent recombination with electron trapping centres released energy, thereby resulting in excitation of luminescent centres. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
17.
D. A. Peterson J. M. Gerrard 《Redox report : communications in free radical research》2013,18(4):303-305
Zinc has been shown to inhibit β-receptor activation of adenylate cyclase at a post receptor site. We have postulated that the β-receptor is one of several receptors activated by reduction, followed by transmembrane elector transfer accelerated by GTP. GTP accelerates electron transfer in a model system and this accelerated electron transfer is inhibited by zinc. This could explain the mechanism of the post receptor inhibition by zinc of the adenylate cyclase stimulation which follows β-receptor activation. 相似文献
18.
Bin Jiang Jeffrey Mason Anahid Jewett Jun Qian Yijiang Ding William CS Cho Xichen Zhang Yan-gao Man 《International journal of biological sciences》2013,9(1):119-133
Background: Colorectal carcinogenesis is believed to be a multi-stage process that originates with a localized adenoma, which linearly progresses to an intra-mucosal carcinoma, to an invasive lesion, and finally to metastatic cancer. This progression model is supported by tissue culture and animal model studies, but it is difficult to reconcile with several well-established observations, principally among these are that up to 25% of early stage (Stage I/II), node-negative colorectal cancer (CRC) develop distant metastasis, and that circulating CRC cells are undetectable in peripheral blood samples of up to 50% of patients with confirmed metastasis, but more than 30% of patients with no detectable metastasis exhibit such cells. The mechanism responsible for this diverse behavior is unknown, and there are no effective means to identify patients with pending, or who are at high risk for, developing metastatic CRC.Novel findings: Our previous studies of human breast and prostate cancer have shown that cancer invasion arises from the convergence of a tissue injury, the innate immune response to that injury, and the presence of tumor stem cells within tumor capsules at the site of the injury. Focal degeneration of a capsule due to age or disease attracts lymphocyte infiltration that degrades the degenerating capsules resulting in the formation of a focal disruption in the capsule, which selectively favors proliferating or “budding” of the underlying tumor stem cells. Our recent studies suggest that lymphocyte infiltration also triggers metastasis by disrupting the intercellular junctions and surface adhesion molecules within the proliferating cell buds causing their dissociation. Then, lymphocytes and tumor cells are conjoined through membrane fusion to form tumor-lymphocyte chimeras (TLCs) that allows the tumor stem cell to avail itself of the lymphocyte''s natural ability to migrate and breach cell barriers in order to intravasate and to travel to distant organs. Our most recent studies of human CRC have detected nearly identical focal capsule disruptions, lymphocyte infiltration, budding cells, and the formation of TLCs. Our studies have further shown that age- and type-matched node-positive and -negative CRC have a significantly different morphological and immunohistochemical profile and that the majority of lymphatic ducts with disseminated cells are located within the mucosa adjacent to morphologically normal appearing epithelial structures that express a stem cell-related marker.New hypothesis: Based on these findings and the growth patterns of budding cells revealed by double immunohistochemistry, we further hypothesize that metastatic spread is an early event of carcinogenesis and that budding cells overlying focal capsule disruptions represent invasion- and metastasis-initiating cells that follow one of four pathways to progress: (1) to undergo extensive in situ proliferation leading to the formation of tumor nests that subsequently invade the submucosa, (2) to migrate with associated lymphocytes functioning as “seeds” to grow in new sites, (3) to migrate and intravasate into pre-existing vascular structures by forming TLCs, or (4) to intravasate into vascular structures that are generated by the budding cells themselves. We also propose that only node-positive cases harbor stem cells with the potential for multi-lineage differentiation and unique surface markers that permit intravasation. 相似文献
19.
Sarah C. Atkinson Con Dogovski Matthew T. Downton Peter E. Czabotar Renwick C. J. Dobson Juliet A. Gerrard John Wagner Matthew A. Perugini 《Plant molecular biology》2013,81(4-5):431-446
Lysine is one of the most limiting amino acids in plants and its biosynthesis is carefully regulated through inhibition of the first committed step in the pathway catalyzed by dihydrodipicolinate synthase (DHDPS). This is mediated via a feedback mechanism involving the binding of lysine to the allosteric cleft of DHDPS. However, the precise allosteric mechanism is yet to be defined. We present a thorough enzyme kinetic and thermodynamic analysis of lysine inhibition of DHDPS from the common grapevine, Vitis vinifera (Vv). Our studies demonstrate that lysine binding is both tight (relative to bacterial DHDPS orthologs) and cooperative. The crystal structure of the enzyme bound to lysine (2.4 Å) identifies the allosteric binding site and clearly shows a conformational change of several residues within the allosteric and active sites. Molecular dynamics simulations comparing the lysine-bound (PDB ID 4HNN) and lysine free (PDB ID 3TUU) structures show that Tyr132, a key catalytic site residue, undergoes significant rotational motion upon lysine binding. This suggests proton relay through the catalytic triad is attenuated in the presence of lysine. Our study reveals for the first time the structural mechanism for allosteric inhibition of DHDPS from the common grapevine. 相似文献
20.
Stephen E. Gerrard Alyssa M. Larson Alexander M. Klibanov Nigel K.H. Slater Carl V. Hanson Barbara F. Abrams Mary K. Morris 《Biotechnology and bioengineering》2013,110(7):2058-2062
The infectivity of high‐titer, cell‐free HIV in culture media and human milk is rapidly reduced upon exposure to polyethylene slides painted with the linear hydrophobic polycation N,N‐dodecyl,methyl‐polyethylenimine (DMPEI). Accompanying viral p24 protein and free viral RNA analysis of solutions exposed to DMPEI‐coated surfaces suggests that virion attachment to the polycationic surface and its subsequent inactivation are the likely mechanism of this phenomenon. Biotechnol. Bioeng. 2013; 110: 2058–2062. © 2013 Wiley Periodicals, Inc. 相似文献