全文获取类型
收费全文 | 383篇 |
免费 | 32篇 |
国内免费 | 16篇 |
出版年
2023年 | 2篇 |
2022年 | 2篇 |
2021年 | 9篇 |
2020年 | 8篇 |
2019年 | 8篇 |
2018年 | 9篇 |
2017年 | 5篇 |
2016年 | 10篇 |
2015年 | 15篇 |
2014年 | 14篇 |
2013年 | 21篇 |
2012年 | 12篇 |
2011年 | 19篇 |
2010年 | 18篇 |
2009年 | 16篇 |
2008年 | 15篇 |
2007年 | 12篇 |
2006年 | 18篇 |
2005年 | 16篇 |
2004年 | 22篇 |
2003年 | 18篇 |
2002年 | 8篇 |
2001年 | 12篇 |
2000年 | 9篇 |
1999年 | 12篇 |
1998年 | 9篇 |
1997年 | 11篇 |
1996年 | 6篇 |
1995年 | 10篇 |
1994年 | 11篇 |
1993年 | 15篇 |
1992年 | 10篇 |
1991年 | 9篇 |
1990年 | 6篇 |
1989年 | 7篇 |
1988年 | 3篇 |
1987年 | 2篇 |
1986年 | 2篇 |
1985年 | 5篇 |
1984年 | 4篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1977年 | 2篇 |
排序方式: 共有431条查询结果,搜索用时 15 毫秒
361.
Florentyna Lustig Johan Hoebeke Carolina Simonson Gunnel
stergren‐Lundn Gran Bondjers Ulla Rüetchi Gunnar Fager 《Journal of molecular recognition : JMR》1999,12(2):112-120
The platelet derived growth factor (PDGF), a mitogen for mesenchymal cells, may be bound to and inhibited by heparin and other glycosaminoglycans. PDGF is a homo‐ or heterodimer of A‐ and B‐chains. They occur as short (A109 and B110) and long (A125 and B160) isoforms. The latter contain basic carboxyl‐terminal extensions. Dimeric A125 binds to heparin through its basic extension in a two‐step reaction. The mechanism involves a conformational change and is consistent with a Monod–Wyman–Changeux allosteric model. Previous indirect experiments suggested that three critical amino acids (basic R111, K116 and polar T125) might be involved. Here, direct binding experiments using dimeric full‐length mutants in surface plasmon resonanse analysis showed that all three critical amino acids in an R(X)4K(X)8T‐motif contributed in a concerted manner to the high affinity binding. Mutations of these amino acids to alanine resulted in large thermodynamic changes, loss of the allosteric mechanism and order(s) of magnitude lower binding affinity. The binding mechanism and affinity of long dimeric rB were similar to the mutants. Short dimeric rA109 and rB110 showed 100 times lower binding affinity than rA125. Consequently, interactions with glycosaminoglycans in tissues varies between PDGF isoforms and may influence their local accumulation and activity. Copyright © 1999 John Wiley & Sons, Ltd. 相似文献
362.
Glycosaminoglycans (GAGs) were reported to induce acrosome reactions (AR) in epididymal and ejaculated bovine sperm (4,5). The GAGs chondroitin sulfate A (CS-A) and heparin were tested on ejaculated bovine sperm for their ability to increase in vitro fertilization (IVF) frequencies. Regardless of treatment, a sperm-egg incubation time of 18 hr was sufficient to achieve maximal rates of fertilization. The IVF frequency of sperm incubated 6 hr with 10 mug/ml heparin (116 173 , 67%) was increased (P<0.05) above control levels (56 181 , 31%); however, 10 mug/ml CS-A (56 164 , 34%) was without effect (P>0.05). In contrast to previous reports, CS-A did not (P>0.05) induce AR in ejaculated (9.5-hr incubation) or epididymal sperm (22.5-hr incubation). Linear increases in fertilization frequency (40% to 81%; P=0.001) and AR (9% to 32%; P=0.05) occurred with time of sperm exposure to heparin (15 sec to 6 hr) suggesting a direct effect of heparin on sperm. Glucose interfered with the effect of heparin on sperm. These data show heparin can prepare sperm for AR and fertilization in vitro and suggest that heparin-like material present in the female bovine reproductive tract may play a role in vivo in sperm capacitation and fertilization. 相似文献
363.
Chin N. Lee Richard R. Handrow Richard W. Lenz Roy L. Ax 《Molecular reproduction and development》1985,12(4):345-355
Previous reports indicate that glycosaminoglycans (GAGs) would enhance the occurrence of acrosome reactions in sperm in vitro, but continuous exposure of those sperm to seminal plasma prevented a significant incidence of acrosome reactions. This study was designed to evaluate the interaction of GAGs and seminal plasma to promote acrosome reactions in bull sperm in vitro. Epididymal sperm required 22 hr to exhibit acrosome reactions in response to GAGs whereas only 9 hr were needed to achieve the same effect with washed ejaculated sperm. Exposure of epididymal sperm to seminal plasma for 20 min shortened the time for induction of the acrosome reaction to 9 hr. Scatchard analyses of displacement data suggested an alteration in the binding affinity of 3H-heparin to epididymal sperm membrane following the short-term exposure to seminal plasma. High doses (250 and 500 μg/ml) of heparin, heparan sulfate, and chondroitin-4-sulfate were without effect, but doses <100 μg/ml were stimulatory in terms of enhancing acrosome reactions. Compositional studies with seminal plasma revealed a total GAG content of 1.6 mg/ml, proportioned as 61.6% chondroitin sulfates, 17.6% heparin-like material, 0.3% hyaluronic acid, and 20.5% undetermined GAG. It is proposed that seminal plasma can alter the ability of sperm to respond to GAGs, and the high concentrations of GAGs endogenous to seminal plasma may prevent premature initiation of the membrane perturbations necessary for the acrosome reaction. 相似文献
364.
Histochemical data are presented verifying the presence of heparin in mast cells of the traira, Hoplias malabaricus . 相似文献
365.
Summary The effects on the cytosolic Ca2+ concentration of activating cholecystokinin receptors on single mouse pancreatic acinar cells have been investigated using patch-clamp whole-cell recording of Ca2+-dependent Cl– current. We used the nonsulphated octapeptide of cholecystokinin (CCK8-NS) since the effects of even high concentrations were rapidly reversible which was not the case for the sulphated octapeptide. A submaximal concentration of CCK8-NS (10nm) evoked a current response consisting of short-lasting (a few seconds) spikes, and some of these spikes were seen to trigger larger and longer (about half a minute) current pulses. At a higher concentration (100nm) CCK8-NS evoked smooth and sustained responses. The effect of CCK8-NS was almost abolished when the internal perfusion solution contained a high concentration of the Ca2+ chelator EGTA (5mm). The responses evoked by CCK8-NS were independent of the presence of Ca2+ in the external solution at least for the first 5 min of stimulation. Internal perfusion with GTP--S markedly potentiated the effect of CCK8-NS or at a higher concentration itself induced responses very similar to those normally evoked by CCK8-NS. Caffeine added to the external solution at a low concentration (0.2–1mm) enhanced weak CCK8-NS responses, whereas high caffeine concentrations always inhibited the CCK8-NS-evoked responses. These inhibitory caffeine effects were quickly reversible. Forskolin evoked a similar inhibitory effect. Intracellular heparin (200 g/ml) infusion markedly inhibited the response to CCK8-NS stimulation. We conclude that the primary effect of activating CCK receptors is to induced inositoltrisphosphate (IP3) production. IP3 evokes a small and steady Ca2+ release, and this in turn evokes pulsatile release of a larger magnitude from a caffeine-sensitive Ca2+ pool. The action of CCK is thus very similar to that previously established for muscarinic receptor activation in the same cells. Nevertheless, the pattern of the cytosolic Ca2+ fluctuations are different, and the basic process of Ca2+-induced Ca2+ release and Ca2+ signal spreading must therefore be modulated by a messenger yet unknown. 相似文献
366.
Heparan sulphate is a potent inhibitor of DNA synthesis in vitro 总被引:4,自引:0,他引:4
D J Winterbourne J G Salisbury 《Biochemical and biophysical research communications》1981,101(1):30-37
The nature and the role of eIF-2 phosphoprotein phosphatase in rabbit reticulocyte lysates have been examined. The eIF-2 phosphoprotein phosphatase is inhibited by a variety of divalent metal ions (Cd++>Ag++> Cu++>Pb++>Zn++>Co++>Sr++>Mo++) in lysates . In addition, PPi, EDTA and NaF inhibit this enzyme. The eIF-2 phosphoprotein phosphatase is also inhibited by NaHSO3 and Na2S2O5. Na2S2O5 is, however, more effective. Na2S2O5 has been found to be a potent inhibitor of protein synthesis in lysates. This inhibition is associated with the phosphorylation of the 38,000-dalton subunit of initiation factor eIF-2. eIF-2 overcomes this inhibition. These findings suggest that under optimum conditions of protein synthesis the phosphorylation and dephosphorylation of eIF-2 are in a dynamic state of equilibrium in which dephosphorylation is favored. The inhibition of eIF-2 phosphoprotein phosphatase by Na2S2O5 shifts this equilibrium in favor of eIF-2 phosphorylation, consequently, protein synthesis is inhibited. The sulfhydryl nature of eIF-2 phosphoprotein phosphatase has been established. 相似文献
367.
成纤维细胞生长因子(FGFs)对于细胞代谢的刺激作用是通过双受体系统(dual-receptor system)介导的.该系统包括一个酪氨酸激酶受体家族(FGFRs)及肝素硫酸蛋白多糖(HSPG).目前已知有4种FGFRs基因,其转录过程表现出剪切多样性.FGFs与FGFRs的结合表现出交叉特异性.HSPG可促进FGFs与FGFRs的结合和受体二聚体的形成,并增强FGFs对细胞调控的精度.FGFRs通过激活不同下游信号分子影响细胞有丝分裂、神经细胞轴突生长、胚胎发育等. 相似文献
368.
Lisa Kinsella Hai-Lan Chen John A Smith Philip S Rudland David G Fernig 《Glycoconjugate journal》1998,15(4):419-422
We have examined structure-function relationships that have been proposed to account for the heparin-binding properties of basic fibroblast growth factor and its receptor, FGFR-1, using synthetic peptides, DNA synthesis assays and binding assays in a resonant mirror biosensor. The results suggest that the interaction of FGFR-1 with heparin may not be physiologically relevant and that the site of interaction of the polysaccharide on bFGF is more complex than has been anticipated. © 1998 Rapid Science Ltd 相似文献
369.
370.
M. S. Pepper J.-D. Vassalli L. Orci R. Montesano J. W. Wilks L. Schweigerer 《Journal of cellular biochemistry》1994,55(4):419-434
A tightly controlled increase in extracellular proteolysis, restricted both in time and space, is an important component of the angiogenic process, while anti-proteolysis is effective in inhibiting angiogenesis. By focussing on the plasminogen activator (PA)-plasmin system, the objective of the present studies was to assess whether previously described inhibitors of angiogenesis modify bovine microvascular endothelial cell proteolytic properties. We demonstrate that although synthetic angiostatic steroids (U-24067 and U-42129), heparin, suramin, interferon alpha-2a, and retinoic acid are all inhibitors of in vitro angiogenesis, each of these agents has distinct effects on the plasminogen-dependent proteolytic system. Specifically, angiostatic steroids and interferon alpha-2a reduce urokinase-type PA (u-PA) and PA inhibitor-1 activity, while heparin and retinoic acid increase u-PA activity. Suramin reduces cell-associated u-PA activity and greatly increases PAI-1 production at doses which induce monolayer disruption. These findings demonstrate that a spectrum of alterations in extracellular proteolysis is associated with anti-angiogenesis, and that anti-angiogenesis and anti-proteolysis are not necessarily correlated. A reduction in extracellular proteolysis would be expected to reduce invasion, whereas an increase in proteolysis might modulate the activity of inhibitory cytokines, which in turn could reduce endothelial cell proliferation and migration and inhibit angiogenesis. The spectrum of effects on different elements of the PA system observed in response to the agents assessed suggests that the role of modulations in extracellular proteolytic activity in anti-angiogenesis is likely to be varied and complex. © 1994 Wiley-Liss, Inc. 相似文献