全文获取类型
收费全文 | 570篇 |
免费 | 15篇 |
国内免费 | 39篇 |
专业分类
系统科学 | 11篇 |
丛书文集 | 15篇 |
教育与普及 | 1篇 |
现状及发展 | 92篇 |
综合类 | 503篇 |
自然研究 | 2篇 |
出版年
2023年 | 4篇 |
2022年 | 2篇 |
2021年 | 6篇 |
2020年 | 8篇 |
2019年 | 8篇 |
2018年 | 8篇 |
2017年 | 8篇 |
2016年 | 11篇 |
2015年 | 24篇 |
2014年 | 26篇 |
2013年 | 18篇 |
2012年 | 31篇 |
2011年 | 25篇 |
2010年 | 20篇 |
2009年 | 36篇 |
2008年 | 26篇 |
2007年 | 40篇 |
2006年 | 27篇 |
2005年 | 31篇 |
2004年 | 41篇 |
2003年 | 23篇 |
2002年 | 19篇 |
2001年 | 16篇 |
2000年 | 10篇 |
1999年 | 25篇 |
1998年 | 18篇 |
1997年 | 14篇 |
1996年 | 11篇 |
1995年 | 5篇 |
1994年 | 8篇 |
1993年 | 14篇 |
1992年 | 11篇 |
1991年 | 9篇 |
1990年 | 8篇 |
1989年 | 12篇 |
1988年 | 7篇 |
1987年 | 7篇 |
1986年 | 4篇 |
1985年 | 1篇 |
1984年 | 2篇 |
排序方式: 共有624条查询结果,搜索用时 15 毫秒
431.
Rose P Whiteman M Huang SH Halliwell B Ong CN 《Cellular and molecular life sciences : CMLS》2003,60(7):1489-1503
-Phenylethyl isothiocyanate (PEITC) is a promising chemoprotective compound that is
routinely consumed in the diet as its glucosinolate precursor. Previous studies have shown that PEITC
can inhibit phase I enzymes and induce phase II detoxification enzymes along with apoptosis in vitro.
The detailed mechanisms involved in the apoptotic cascade, however, have not been elucidated. In the
present study, we demonstrate that PEITC can induce apoptosis in hepatoma HepG2 cells in a
concentration- and time-dependant manner as determined by TUNEL positive and SubG1 population
analysis. Caspase-3-like activity and poly(ADP-ribosyl)polymerase cleavage increased during
treatment with 20 µM PEITC; high concentrations, however, induced necrosis. Pre-treatment with
Z-VAD-FMK and the caspase-3-specific inhibitor Ac-DEVD-CHO prevented PEITC-induced apoptosis, as
determined by caspase-3-like activity and DNA fragmentation. Additional investigations also showed
that at concentrations of 5-C10 µM PEITC, DNA synthesis was inhibited and G2/M phase cell cycle
arrest occurred, correlating with an alteration in cyclin B1 and p34cdc2 protein levels. Furthermore, we also demonstrate
a concentration- and time-dependant burst of superoxide (O2-)
in PEITC-treated cells. However, pre- and co-treatment with the free radical scavengers Trolox,
ascorbate, mannitol, uric acid and the superoxide mimetic manganese (III) tetrakis (N-methyl-2-pyridyl)
porphyrin failed to prevent PEITC-mediated apoptosis. Taken together, these results suggest that
PEITC potently induces apoptosis and cell cycle arrest in HepG2 cells and that the
generation of reactive oxygen species appears to be a secondary effect.Received 23 December 2002; accepted 22 April 2003 相似文献
432.
ERKs are the point of divergence of PKA and PKC activation by PTHrP in human skin fibroblasts 总被引:3,自引:0,他引:3
Fortino V Torricelli C Gardi C Valacchi G Rossi Paccani S Maioli E 《Cellular and molecular life sciences : CMLS》2002,59(12):2165-2171
Parathyroid hormone-related peptide (PTHrP) receptors, coupled to trimeric G proteins, operate in most target cells through
at least three different transduction routes: Gαs-mediated stimulation of adenylylcyclase (AC), Gαq-mediated activation of
phospholipase Cβ (PLC) and mitogen-activated protein kinase (MAPK) activation. In this study we investigated the relative
role of different pathways in human skin fibroblast prolifera-tion. Using chemical inhibitors and activators of signal transduction,
we demonstrated that: (i) AC/cAMP and PLC/1,4,5 inositol triphosphate/diacylglycerol second-messenger systems are simultaneously
activated following PTHrP binding to its receptors; (ii) the mitogenic response to PTHrP derives from a balance between two
counteracting pathways – an activating route mediated by protein kinase C (PKC) and an inhibitory route mediated by protein
kinase A (PKA); (iii) PTHrP mitogenic effects are largely dependent on MAPKs, whose activity can be modulate
d by both PKA and PKC. Our results indicate that MAPKs are common targets of both transduction routes and, at the same time,
their point of divergence in mediating PTHrP dual and opposite mitogenic effects.
Received 2 August 2002; received after revision 10 September 2002; accepted 18 October 2002
RID="*"
ID="*"Corresponding author. 相似文献
433.
本文针对IBM Cell/B.E 模拟环境的构建提出了一种借助Shell脚本创建的方法,解决了模拟环境构建中所面临的图形系统的自动启动与配置、License的自动确认、软件的自动安装与配置等问题,并给出了实例测试验证该方法的正确性.这为今后研究和使用IBM Cell/B.E模拟环境提供了一种尝试性的解决方案. 相似文献
434.
D. S. Richard A. E. Arnim L. I. Gilbert 《Cellular and molecular life sciences : CMLS》1993,49(2):150-156
The histolysis of larval fat body cells in adult femaleDrosophila melanogaster was examined in wild type and mutant animals. The fat body cells of wild type (Canton-S),apterous
56f homozygotes,apterous
78jts homozygotes and heterozygotes,apterous
4/+, ecdysoneless1 homozygotes and heterozygotes all underwent histolysis normally during the 72 h following adult eclosion. Only in the case ofap
4/ap4 adults did the cells fail to histolyze normally. The fat body cells of both diapausing and non-diapausing wild type females underwent histolysis at the same rate. Attempts to demonstrate histolysis in vitro were unsuccessful, even in the presence of juvenile hormones (JHs), larval ring glands, or adult ovaries. In all strains other than theap
4 homozygotes, a significant proportion of larval fat body cells were dead at any time while theap
4/ap4 animals, almost all cells remained viable. It is postulated that fat body cell lysis following eclosion is not a JH-mediated event, but is elicited by an as yet unidentified factor(s), possibly originating in the ovary. 相似文献
435.
这种传感器的细胞固定化是左氢电极膜表面紧贴一层包埋着茁芽丝孢酵母的海藻胶层,再在凝胶层上覆盖一片透析膜,该传感器的基本特性除类似或略优于透析膜包装的传感器外,还具有两个很重要的特点:稳定性高,可反复使用3个月以上;便于培养处理,使因热或化学因子而失活的传感器获得再生。 相似文献
436.
N. Hamilton M. L. Ashton C. D. Ianuzzo 《Cellular and molecular life sciences : CMLS》1991,47(10):1070-1072
Morphological characteristics of myocardial ventricular myocytes have been evaluated from 5 mammalian orders with resting heart rates ranging from 51 to 475 bpm. The purpose was to determine if morphological characteristics of the myocardia are related to the functional demand imposed on the cell as represented by the resting heart rate. Cell size is a constant among mammals of different sizes which have different physiological demands. In contrast, there is more mitochondrial area and less myofibrillar area per cell in animals with rapidly beating hearts than in animals with slower heart rates. Additionally, the mean cross sectional area of individual myofibrils is 30% larger in the cow as compared to the mouse. These findings combined with our previous studies indicate that the different functional requirements of myocardia from different mammalian orders are satisfied by intracellular adaptations of both a structural and biochemical nature. 相似文献
437.
Bryja V Pacherník J Soucek K Horvath V Dvorák P Hampl A 《Cellular and molecular life sciences : CMLS》2004,61(11):1384-1400
In mouse embryonic stem (mES) cells, the expression of p27 is elevated when differentiation is induced. Using mES cells lacking p27 we tested the importance of p27 for the regulation of three critical cellular processes: proliferation, differentiation, and apoptosis. Although cell cycle distribution, DNA synthesis, and the activity of key G1/S-regulating cyclin-dependent kinases remained unaltered in p27-deficient ES cells during retinoic acid-induced differentiation, the amounts of cyclin D2 and D3 in such cells were much lower compared with normal mES cells. The onset of differentiation induces apoptosis in p27-deficient cells, the extent of which can be reduced by artificially increasing the level of cyclin D3. We suggest that the role of p27 in at least some differentiation pathways of mES cells is to prevent apoptosis, and that it is not involved in slowing cell cycle progression. We also propose that the pro-survival function of p27 is realized via regulation of metabolism of D-type cyclin(s).Received 25 February 2004; received after revision 5 April 2004; accepted 15 April 2004 相似文献
438.
Opposite roles of protein kinase C isoforms in proliferation, differentiation, apoptosis, and tumorigenicity of human HaCaT keratinocytes 总被引:2,自引:0,他引:2
Papp H Czifra G Bodó E Lázár J Kovács I Aleksza M Juhász I Acs P Sipka S Kovács L Blumberg PM Bíró T 《Cellular and molecular life sciences : CMLS》2004,61(9):1095-1105
We have previously shown that the protein kinase C (PKC) system plays a pivotal role in regulation of proliferation and differentiation of the human keratinocyte line HaCaT which is often used to assess processes of immortalization, transformation, and tumorigenesis in human skin. In this paper, using pharmacological and molecular biology approaches, we investigated the isoform-specific roles of certain PKC isoenzymes (conventional cPKC and ; novel nPKC and ) in the regulation of various keratinocyte functions. cPKC and nPKC stimulated cellular differentiation and increased susceptibility of cells to actions of inducers of apoptosis, and they markedly inhibited cellular proliferation and tumor growth in immunodeficient mice. In marked contrast, cPKC and nPKC increased both in vitro and in vivo growth of cells and inhibited differentiation and apoptosis. Our data present clear evidence for the specific, antagonistic roles of certain cPKC and nPKC isoforms in regulating the above processes in human HaCaT keratinocytes.Received 13 January 2004; received after revision 18 February 2004; accepted 25 February 2004 相似文献
439.
端粒和端粒酶是现代生物学研究的热点,端粒的缺失与细胞的衰老,端粒酶的活性与细胞的老化及癌化均有密切的关系.文章综述了端粒和端粒酶的结构和功能及其与细胞衰老及肿瘤的关系,并在此基础之上展望了端粒酶在抗衰老、抑制肿瘤等方面的应用. 相似文献
440.