全文获取类型
收费全文 | 17302篇 |
免费 | 1279篇 |
国内免费 | 199篇 |
出版年
2024年 | 17篇 |
2023年 | 68篇 |
2022年 | 52篇 |
2021年 | 372篇 |
2020年 | 256篇 |
2019年 | 353篇 |
2018年 | 511篇 |
2017年 | 391篇 |
2016年 | 648篇 |
2015年 | 945篇 |
2014年 | 1113篇 |
2013年 | 1187篇 |
2012年 | 1569篇 |
2011年 | 1485篇 |
2010年 | 956篇 |
2009年 | 788篇 |
2008年 | 1122篇 |
2007年 | 984篇 |
2006年 | 905篇 |
2005年 | 830篇 |
2004年 | 778篇 |
2003年 | 648篇 |
2002年 | 516篇 |
2001年 | 448篇 |
2000年 | 381篇 |
1999年 | 288篇 |
1998年 | 120篇 |
1997年 | 104篇 |
1996年 | 74篇 |
1995年 | 74篇 |
1994年 | 55篇 |
1993年 | 44篇 |
1992年 | 104篇 |
1991年 | 71篇 |
1990年 | 59篇 |
1989年 | 61篇 |
1988年 | 41篇 |
1987年 | 41篇 |
1986年 | 33篇 |
1985年 | 35篇 |
1984年 | 22篇 |
1983年 | 20篇 |
1982年 | 21篇 |
1981年 | 18篇 |
1980年 | 20篇 |
1979年 | 17篇 |
1978年 | 17篇 |
1975年 | 18篇 |
1974年 | 14篇 |
1971年 | 10篇 |
排序方式: 共有10000条查询结果,搜索用时 875 毫秒
991.
992.
We investigated the fragmentation of human ceruloplasmin induced by H2O2 to study its oxidative damage. When ceruloplasmin was incubated with H2O2, the frequency of the protein fragmentation increased in a proportion to the concentration of H2O2. It also increased in a time-dependent manner and was accompanied by gradual loss of the oxidase activity. Hydroxyl radical scavengers such as azide and mannitol inhibited the fragmentation of ceruloplasmin. The deoxyribose assay showed that hydroxyl radicals were generated in the reaction of ceruloplasmin with H2O2. Incubation of ceruloplasmin with H2O2 resulted in a time-dependent release of copper ions. The released copper ion may participate in a Fenton-like reaction to produce hydroxyl radical, which enhanced the fragmentation. The protection of the fragmentation by copper chelators such as diethylenetriaminepentaacetic acid and bathocuproine indicates a role for copper ion in the reaction. These results suggest that the fragmentation of ceruloplasmin induced by H2O2 is due to hydroxyl radicals formed by a copper-dependent Fenton-like reaction. 相似文献
993.
A new cry1I-type gene, cry1Id1, was cloned from a B. thuringiensis isolate, and its nucleotide sequence was determined. The deduced amino acid sequence of Cry1Id1 is 89.7%, 87.2%, and 83.4%
identical to the Cry1Ia, Cry1Ib, and Cry1Ic proteins, respectively. The upstream sequence of the cry1Id1 structural gene was not functional as promoter in B. subtilis. The Cry1Id1 protein, purified from recombinant E. coli cells, had a toxicity comparable to that of Cry1Ia against Plutella xylostella, but it was significantly less active than Cry1Ia against Bombyx mori. Cry1Id1 was not active against the coleopteran insect, Agelastica coerulea.
Received: 19 January 2000 / Accepted: 22 February 2000 相似文献
994.
Choi J Liu RM Kundu RK Sangiorgi F Wu W Maxson R Forman HJ 《The Journal of biological chemistry》2000,275(5):3693-3698
Human immunodeficiency virus (HIV) progressively depletes GSH content in humans. Although the accumulated evidence suggests a role of decreased GSH in the pathogenesis of HIV, significant controversy remains concerning the mechanism of GSH depletion, especially in regard to envisioning appropriate therapeutic strategies to help compensate for such decreased antioxidant capacity. Tat, a transactivator encoded by HIV, is sufficient to cause GSH depletion in vitro and is implicated in AIDS-associated Kaposi's sarcoma and B cell lymphoma. In this study, we report a decrease in GSH biosynthesis with Tat, using HIV-1 Tat transgenic (Tat+) mice. A significant decline in the total intracellular GSH content in liver and erythrocytes of Tat+ mice was accompanied by decreased gamma-glutamylcysteine synthetase regulatory subunit mRNA and protein content, which resulted in an increased sensitivity of gamma-glutamylcysteine synthetase to feedback inhibition by GSH. Further study revealed a significant reduction in the activity of GSH synthetase in liver of Tat+ mice, which was linearly associated with their GSH content. Therefore, Tat appears to decrease GSH in vivo, at least partially, through modulation of GSH biosynthetic enzymes. 相似文献
995.
Shim J Park HS Kim MJ Park J Park E Cho SG Eom SJ Lee HW Joe CO Choi EJ 《The Journal of biological chemistry》2000,275(19):14107-14111
The Rb protein is the product of the retinoblastoma susceptibility gene and loss of Rb function is detected in many types of human cancers. Rb plays important roles in the regulation of cell proliferation, differentiation, senescence, and apoptotic cell death. Here we show that Rb can physically interact with c-Jun NH(2)-terminal kinase/stress-activated protein kinase (JNK/SAPK), thereby inhibiting intracellular signals mediated by JNK/SAPK. Both in vitro binding and in vitro kinase studies suggest that a carboxyl-terminal domain of Rb containing amino acids 768-928 might be crucial for inhibiting JNK/SAPK. In comparison, Rb did not affect enzymatic activity of either extracellular signal-regulated kinase 1 or p38. Ectopically expressed Rb also abrogated the apoptotic cell death induced by ultraviolet radiation or the activation of MEKK1, an upstream kinase that can stimulate the JNK/SAPK cascade. JNK/SAPK inhibition highlights a novel function of Rb, which may provide a new mechanism by which Rb regulates cell death. JNK/SAPK is a major protein kinase that can be stimulated in response to a variety of cellular stresses. Our results, therefore, suggest that Rb, by inhibiting JNK/SAPK, may act as a negative regulator in stress-activated intracellular signaling cascades. 相似文献
996.
997.
Chen J Wang Y Nakajima T Iwasawa K Hikiji H Sunamoto M Choi DK Yoshida Y Sakaki Y Toyo-Oka T 《The Journal of biological chemistry》2000,275(37):28739-28749
The rise in cytosolic Ca(2+) concentration (Ca(2+)(i)) in vascular endothelial cells (ECs) activates the production and release of nitric oxide (NO). NO modifies Ca(2+)(i) homeostasis in many types of nonendothelial cells. However, its effect on endothelial Ca(2+)(i) homeostasis at basal and excited states remains unclear. In the present study, to elucidate the effect of NO on basal Ca(2+)(i), inositol 1,4,5-trisphosphate-induced Ca(2+)(i) release (IICR) was blocked by expressing an antisense against type-1 inositol 1,4,5-trisphosphate receptors or by microinjecting heparin to individual ECs, and the effects of NO that was released by and diffused from adjacent IICR-intact ECs were recorded. After ATP or bradykinin stimulation, IICR-inhibited ECs showed a marked reduction of basal Ca(2+)(i), which was abolished by N(G)-monomethyl-l-arginine monoacetate pretreatment. The reduction disappeared in sparsely seeded ECs. Exogenous NO gas mimicked the effect of ATP or bradykinin to reduce basal Ca(2+)(i). Blocking plasma membrane Ca(2+)-ATPase (PMCA), but not Na(+)-Ca(2+) exchange or sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase, suppressed the reduction, indicating that the reduction resulted from a NO-dependent potentiation of PMCA. To elucidate the effect of NO on elevated Ca(2+)(i), ATP-, bradykinin-, or thapsigargin-evoked Ca(2+)(i) response in the presence and absence of NO production was compared in adjacent IICR-intact ECs. NO was found to potentiate PMCA, which, in turn, greatly attenuated agonist-evoked Ca(2+)(i) elevation. NO also potentiated Ca(2+) influx, which markedly increased the sustained phase of Ca(2+)(i) elevation and possibly NO production. NO did not affect other Ca(2+)(i)-elevating and Ca(2+)(i)-sequestrating components. Thus, NO-dependent potentiation of PMCA is crucial for Ca(2+)(i) homeostasis over a wide Ca(2+)(i) range. 相似文献
998.
Jew SS Yoo CH Lim DY Kim H Mook-Jung I Jung MW Choi H Jung YH Kim H Park HG 《Bioorganic & medicinal chemistry letters》2000,10(2):119-121
8 Semi-synthetic derivatives of asiatic acid were prepared and their protective effect against A beta-induced neurotoxicity was evaluated. Among them, asiatic acid (2), and 4, 16 showed 97, 92 and 87% of protective effect, respectively. 相似文献
999.
1000.
The distribution and requirements of microtubules and microfilaments in bovine oocytes during in vitro maturation 总被引:1,自引:0,他引:1
Microtubules and microfilaments are major cytoskeletal components and important modulators for chromosomal movement and cellular division in mammalian oocytes. In this study we observed microtubule and microfilament organisation in bovine oocytes by laser scanning confocal microscopy, and determined requirements of their assembly during in vitro maturation. After germinal vesicle breakdown, small microtubular asters were observed near the condensed chromatin. The asters appeared to elongate and encompass condensed chromatin particles. At the metaphase stage, microtubules were observed in the second meiotic spindle at the metaphase stage. The meiotic spindle was a symmetrical, barrel-shaped structure containing anastral broad poles, located peripherally and radially oriented. Treatment with nocodazole did not inhibit germinal vesicle breakdown. However, progression to metaphase failed to occur in oocytes treated with nocodazole. In contrast, microfilaments were observed as a relatively thick uniform area around the cell cortex and overlying chromatin following germinal vesicle breakdown. Treatment with cytochalasin B inhibited microfilament polymerisation but did not prevent either germinal vesicle breakdown or metaphase formation. However, movement of chromatin to the proper position was inhibited in oocytes treated with cytochalasin B. These results suggest that both microtubules and microfilaments are closely associated with reconstruction and proper positioning of chromatin during meiotic maturation in bovine oocytes. 相似文献