全文获取类型
收费全文 | 310篇 |
免费 | 4篇 |
国内免费 | 20篇 |
专业分类
丛书文集 | 5篇 |
教育与普及 | 2篇 |
现状及发展 | 127篇 |
综合类 | 200篇 |
出版年
2023年 | 1篇 |
2022年 | 1篇 |
2020年 | 3篇 |
2019年 | 4篇 |
2018年 | 2篇 |
2017年 | 6篇 |
2016年 | 5篇 |
2015年 | 9篇 |
2014年 | 4篇 |
2013年 | 5篇 |
2012年 | 11篇 |
2011年 | 11篇 |
2010年 | 6篇 |
2009年 | 15篇 |
2008年 | 13篇 |
2007年 | 15篇 |
2006年 | 28篇 |
2005年 | 29篇 |
2004年 | 19篇 |
2003年 | 17篇 |
2002年 | 18篇 |
2001年 | 14篇 |
2000年 | 9篇 |
1999年 | 15篇 |
1998年 | 10篇 |
1997年 | 4篇 |
1996年 | 13篇 |
1995年 | 5篇 |
1994年 | 6篇 |
1993年 | 4篇 |
1992年 | 2篇 |
1991年 | 4篇 |
1990年 | 3篇 |
1989年 | 7篇 |
1988年 | 3篇 |
1986年 | 3篇 |
1985年 | 8篇 |
1984年 | 2篇 |
排序方式: 共有334条查询结果,搜索用时 726 毫秒
91.
L. De Petrocellis V. Di Marzo G. Cimino 《Cellular and molecular life sciences : CMLS》1993,49(1):57-64
The participation of protein kinase C (PKC) in the regeneration of tentacles ofHydra vulgaris was studied. Regeneration was induced by 1,2-sn-dioctanoyl-glycerol (diC8) and the novel diterpenoidic diacylglycerol verrucosin B (VB), a potent PKC activator extracted from marine sources. VB substantially increasedHydra average tentacle number (ATN) at concentrations 10,000 times lower than those needed for diC8 to exert an analogous effect. When both synthetic and natural VB analogues were tested, the structure/activity relationship found inHydra tentacle regeneration was identical to that known for DAG-induced activation of PKC in vitro. VB-induced increase of ATN was strongly counteracted by the PKC inhibitors sphingosine and A3, but was not synergic with a tenfold increase of extracellular Ca2+ concentration or with an increase of intracellular Ca2+ concentration obtained either with the ionophore A23187 or with thapsigargin. This suggested the involvement of a non-Ca2+-dependent PKC in VB-triggeredHydra tentacle regeneration. The involvement of phospholipase A2 (PLA2) activation inHydra regenerative processes was studied using the novel site-specific inhibitor of the enzyme, oleyloxyethylphosphorylcholine (OOPC), which brought about a striking inhibition of ATN in the low molar range. This effect was reversed by arachidonic acid (AA), while an enhancement of ATN was also observed with an inhibitor of AA uptake from membrane phospholipids, thus suggesting that PLA2-catalysed liberation of AA is involved inHydra tentacle regeneration. OOPC also blocked verrucosin B-induced PKC-mediated enhancement of ATN, thus suggesting that this effect is also mediated by PLA2 activation. ATN was increased also by compound 48/80, a direct activator of pertussis toxin-sensitive GTP-binding proteins, and this effect was counteracted by pertussis toxin pretreatment. None of the known AA cascade inhibitors exhibited an effect on ATN comparable to that exerted by OOPC, but, surprisingly, the cycloxygenase inhibitor indomethacin strongly enhanced ATN, thus suggesting that prostanoids might effect a negative control onHydra regenerative processes. This represents the first attempt so far reported to study the implication of more than one biochemical pathway as a signalling event in the hydroid regenerative processes. 相似文献
92.
利用培养新生大鼠心肌细胞,检测NO前体L-精氨酸(L-arginine,L-Arg)和NO供体硝普钠(sodium nitroprusside,SNP)对PKC活性的影响,并探讨内、外源性NO在PKC激动剂佛波指(phorbol 12-myristate 13-acetate,PMA)激活PKC中的作用.实验结果表明:培养基中加入L-Arg,PKC活性呈剂量依赖性降低;用L-Arg进行预处理,30 min后加入PMA,PKC活性明显降低,与单纯PMA组相比有显著差异;NOS抑制剂L-NAME本身对基础状态PKC活性无明显影响,但可阻断L-Arg对上述2个效应的影响;培养液中加入NO供体SNP,PKC活性呈剂量依赖性降低;用SNP预处理心肌细胞,5 min后加入PMA,PKC活性与单纯PMA组相比有显著性差异.以上结果表明,内、外源性NO均具有剂量依赖性抑制PKC活性的作用,PKC可能是NO对心肌细胞作用的胞内信号传导通路的关键部位或重要信号分子之一;L-Arg通过NOS先生成NO,NO再对PKC起抑制作用. 相似文献
93.
To observe the regulation of platelet-derived growth factor (PDGF) receptor-βin myocyte stimulated by angiotensin II (AngII) at both integrated and cellular levels and reveal the signal transduction mechanism in cell, two kidneys, one clip (2K1C) renal hypertension were performed by placing a sliver clip around the left renal artery. Blood pressure and the ratio of left ventricular weight to body weight were measured at 4 and 8 weeks after operation. The content of AngII in heart was detected by radioimmunology assay; the protein level of PDGF receptor-βin heart was measured by Western blot analysis. The alteration of PDGF receptor-βstimulated by AngII and several inhibitors was observed on cultured neonatal rat ventricular myocyte (NRVM). The content of AngII in heart of 2K1C renal hypertensive rat at 4 and 8 weeks after operation was increased. Compared with sham group, 4 and 8 weeks after operation, PDGF receptor-βin heart of 2K1C group was upregulated by 100.3% and 127.1% (P < 0.05), respectively. This upregulation could be inhibited by captopril. For cultured myocyte, PDGF receptor-βwas increased by 47.1% after being stimulated by AngII and this upregulation could be inhibited by losartan which was an inhibitor of AT1 receptor. PLC inhibitor (U73122) and MEK inhibitor (PD98059) could partly inhibit PDGF receptor-βupregulation induced by AngII. These results suggested that AngII could upregulate PDGF receptor-βin myocyte by its AT1 receptor and this effect was at least partly dependent on PLC and extracellular signal-regulated kinase (ERK). 相似文献
94.
95.
1 Results Selective inhibition of protein tyrosine kinases is gaining importance as an effective therapeutic approach for the treatment of a wide range of human cancers.The epidermal growth factor receptor (EGFR) protein tyrosine kinase is one of the important kinases that play a fundamental role in cell growth signal pathways.We focused on the 4-anilinoquinazoline framework,which is observed in both compounds as a common structure.A boron atom has a vacant orbital and interconverts with ease between th... 相似文献
96.
Oshima T Sasaki M Kataoka H Miwa H Takeuchi T Joh T 《Cellular and molecular life sciences : CMLS》2007,64(23):3139-3147
Tight junctions (TJs) create a paracellular permeability barrier. Although reactive oxygen species have been implicated as
mediators of inflammation in inflammatory bowel diseases, their influence on the function of colonic epithelial TJs remains
unknown. Oxidative stress-mediated colonic epithelial permeability was significantly attenuated by a p38 mitogen-activated
protein (MAP) kinase inhibitor, SB203580. Although the amount of TJ proteins was not altered, hydrogen peroxide (H2O2) changed the localization of claudin-4 protein from an NP-40 insoluble fraction to a soluble fraction and from an apical
TJ to lateral membrane. The p38 MAP kinase inactivator Wip1 significantly attenuated phosphorylation of p38 MAP kinase, and
oxidative stress mediated permeability. H2O2-induced changes in claudin-4 localization were abolished by SB203580 pretreatment as well as Wip1-expressing adenovirus infection.
This is the first study to demonstrate that exogenous Wip1 functions to protect oxidative stress-mediated colonic mucosal
permeability and that H2O2-induced claudin-4 dislocalization is abolished by Wip1.
Received 14 June 2007; received after revision 8 October 2007; accepted 8 October 2007 相似文献
97.
Spindle checkpoint is an important biochemical signaling cascade during mitosis which monitors the fidelity of chromosome
segregation, and is mediated by protein kinases Mps1 and Bub1/BubR1. Our recent studies show that kinesin-related motor protein
CENP-E interacts with BubR1 and participates in spindle checkpoint signaling. To elucidate the molecular mechanisms underlying
spindle checkpoint signaling, we carried out proteomic dissection of human cell kinetochore and revealed protein kinase TTK,
human homologue of yeast Mps1. Our studies show that TTK is localized to the kinetochore of human cells, and interacts with
CENP-E, suggesting that TTK may play an important role in chromosome segregation during mitosis. 相似文献
98.
Krempler A Kartarius S Günther J Montenarh M 《Cellular and molecular life sciences : CMLS》2005,62(12):1379-1387
99.
Ethanol-induced cerebellar hypoplasia is associated with inhibition of insulin-stimulated survival signaling. The present work explores the mechanisms of impaired insulin signaling in a rat model of fetal alcohol syndrome. Real-time quantitative RT-PCR demonstrated reduced expression of the insulin gene in cerebella of ethanol-exposed pups. Although receptor expression was unaffected, insulin and insulin-like growth factor (IGF-I) receptor tyrosine kinase (RTK) activities were reduced by ethanol exposure, and these abnormalities were associated with increased PTP1b activity. In addition, glucose transporter molecule expression and steady-state levels of ATP were reduced in ethanol-exposed cerebellar tissue. Cultured cerebellar granule neurons from ethanol-exposed pups had reduced expression of genes encoding insulin, IGF-II, and the IGF-I and IGF-II receptors, and impaired insulin- and IGF-I-stimulated glucose uptake and ATP production. The results demonstrate that ethanol inhibits insulin-mediated actions in the developing brain by reducing local insulin production and insulin RTK activation, leading to inhibition of glucose transport and ATP production.Received 30 December 2004; received after revision 1 March 2005; accepted 10 March 2005 相似文献
100.
Marchetta M Gamberi T Sarno S Magherini F Raugei G Camici G Pinna LA Modesti A 《Cellular and molecular life sciences : CMLS》2004,61(10):1176-1184
Although the yeast genome does not encode bona fide protein tyrosine kinases, tyrosine-phosphorylated proteins are numerous, suggesting that besides dual-specificity kinases, some Ser/Thr kinases are also committed to tyrosine phosphorylation in Saccharomyces cerevisiae. Here we show that blockage of the highly pleiotropic Ser/Thr kinase CK2 with a specific inhibitor synergizes with the overexpression of Stp1 low-molecular-weight protein tyrosine phosphatase (PTP) in inducing a severe growth-defective phenotype, consistent with a prominent role for CK2 in tyrosine phosphorylation in yeast. We also present in vivo evidence that immunophilin Fpr3, the only tyrosine-phosphorylated CK2 substrate recognized so far, interacts with and is dephosphorylated by Spt1. These data disclose a functional correlation between CK2 and LMW-PTPs, and suggest that reversible phosphorylation of Fpr3 plays a role in the regulation of growth rate and budding in S. cerevisiae.Received 15 January 2004; received after revision 20 February 2004; accepted 4 March 2004 相似文献