全文获取类型
收费全文 | 15298篇 |
免费 | 1733篇 |
国内免费 | 3篇 |
专业分类
17034篇 |
出版年
2022年 | 168篇 |
2021年 | 287篇 |
2020年 | 135篇 |
2019年 | 199篇 |
2018年 | 242篇 |
2017年 | 217篇 |
2016年 | 351篇 |
2015年 | 586篇 |
2014年 | 638篇 |
2013年 | 779篇 |
2012年 | 988篇 |
2011年 | 997篇 |
2010年 | 650篇 |
2009年 | 601篇 |
2008年 | 775篇 |
2007年 | 849篇 |
2006年 | 742篇 |
2005年 | 691篇 |
2004年 | 667篇 |
2003年 | 567篇 |
2002年 | 544篇 |
2001年 | 352篇 |
2000年 | 315篇 |
1999年 | 276篇 |
1998年 | 179篇 |
1997年 | 147篇 |
1996年 | 122篇 |
1995年 | 120篇 |
1994年 | 119篇 |
1993年 | 109篇 |
1992年 | 198篇 |
1991年 | 171篇 |
1990年 | 177篇 |
1989年 | 199篇 |
1988年 | 158篇 |
1987年 | 183篇 |
1986年 | 171篇 |
1985年 | 178篇 |
1984年 | 149篇 |
1983年 | 132篇 |
1982年 | 109篇 |
1981年 | 107篇 |
1979年 | 118篇 |
1978年 | 93篇 |
1977年 | 121篇 |
1976年 | 92篇 |
1974年 | 132篇 |
1973年 | 90篇 |
1971年 | 90篇 |
1969年 | 82篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
1.
Structural requirements for diacylglycerols to mimic tumor-promoting phobol diester action on the epidermal growth factor receptor 总被引:8,自引:0,他引:8
The structural requirements for diacylglycerols to mimic the action of tumor-promoting phorbol diesters on the epidermal growth factor (EGF) receptor of A431 human epidermoid carcinoma cells were investigated. Five biological effects were considered: inhibition of high affinity 125I-EGF binding, change in the phosphorylation state of the EGF receptor, inhibition of the EGF-dependent tyrosine phosphorylation of the EGF receptor, inhibition of [3H]phorbol 12 beta, 13 alpha-dibutyrate binding, and stimulation of calcium- and phospholipid-dependent protein kinase (C-kinase) in vitro. A marked effect of the acyl chain length, 3-10 carbons, of symmetric sn-1,2-diacylglycerols was observed on their ability to mimic the effect of 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA). sn-1,2-Dipropanoylglycerol did not mimic the effects of PMA, but sn-1,2-didecanoylglycerol potently mimicked PMA action. A correlation was found between the ability of these diacylglycerols to stimulate the activity of C-kinase in vitro and to mimic the effects of PMA on the EGF receptor in intact cells. Analogues of sn-1,2-dioctanoylglycerol in which the 3' hydroxyl group was substituted with hydrogen, thio or chloro moieties were inactive when assayed for their ability to stimulate C-kinase in vitro and mimic PMA action in intact cells. We conclude that the hydroxyl group of a diacylglycerol is vital for the interaction with the phorbol diester receptor. The stringent correlation between the potency of the 11 diacylglycerol analogues tested to modulate C-kinase in vitro and to mimic PMA action in vivo provides strong evidence for the hypothesis that C-kinase plays a central role in the regulation of A431 cell EGF receptors by tumor-promoting phorbol diesters. 相似文献
2.
Evidence that the intestinal microbiota is intrinsically linked with overall health, including cancer risk, is emerging. Moreover, its composition is not fixed but can be influenced by several dietary components. Dietary modifiers, including the consumption of live bacteria (probiotics) and indigestible or limited digestible food constituents such as oligosaccharides (prebiotics) and polyphenols or both (synbiotics), are recognized modifiers of the numbers and types of microbes and have been reported to reduce colon cancer risk experimentally. Microorganisms also have the ability to generate bioactive compounds from food components. Examples include equol from isoflavones, enterodiol and enterolactone from lignans and urolithins from ellagic acid, which have also been demonstrated to retard experimentally induced cancers. The gastrointestinal microbiota can also influence both sides of the energy balance equation, namely, as a factor influencing energy utilization from the diet and as a factor that influences host genes that regulate energy expenditure and storage. Because of the link between obesity and cancer incidence and mortality, this complex complexion deserves greater attention. Overall, a dynamic interrelationship exists between the intestinal microbiota and colon cancer risk, which can be modified by dietary components and eating behaviors. 相似文献
3.
4.
J.Kalervo Hiltunen E.Jack Davis 《Biochimica et Biophysica Acta (BBA)/General Subjects》1981,678(1):115-121
The mechanism of depletion of tricarboxylic acid cycle intermediates by isolated rat heart mitochondria was studied using hydroxymalonate (an inhibitor of malic enzymes) and mercaptopicolinate (an inhibitor of phosphoenolpyruvate carboxykinase) as tools. Hydroxymalonate inhibited the respiration rate of isolated mitochondria in state 3 by 40% when 2 mM malate was the only external substrate, but no inhibition was found with 2 mM malate plus 0.5 mM pyruvate as substrates. In the prescence od bicarbonate, arsenite and ATP, propionate was converted to pyruvate and malate at the rates of 14.0 ± 2.9 and 2.8 ± 1.8 nmol/mg protein in 5 min, respectively. Under these conditions, 0.1 mM mercaptopicolinate did not affect this conversion, but 2 mM hydroxymalonate inhibited pyruvate formation completely and resulted in an accumulation of malate up to 13.2 ± 2.9 nmol/mg protein. No accumulation of phosphoenolpyruvate was found under any condition tested. It is concluded that malic enzymes but not phosphoenolpyruvate carboxykinase, are involved in conversion of propionate to pyruvate in isolated rat heart mitochondria. 相似文献
5.
6.
7.
Cell division in fertilized sea urchin eggs was reversibly inhibited when the ketoaldehyde phenyl glyoxal (PG) at a concentration of 0.1 mM was added to eggs for ten minutes prior to the formation of the mitotic spindle. We investigated whether inhibition of mitosis was due to PG binding to the cell surface (as previously suggested by Stein and Berestecky, '74) or to some intracellular effect. When 14C-PG was added to eggs, label was readily taken up into the egg cytoplasm; very little label was associated with the egg surface. In the cytoplasm PG combined with equimolar amounts of reduced glutathione (GSH), decreasing the levels of cellular GSH to less than 15% of normal and accounting for at least 50% of the PG taken up by eggs. The concentrations of oxidized and protein-bound glutathione were unaffected by PG treatment. We showed that glyoxalase enzymes were present in sea urchin eggs and were capable of metabolizing the PG-GSH complex, thereby restoring GSH to normal levels after PG was removed from the sea water. Though some other effect of PG cannot be ruled out, the major fate of PG in eggs was to combine with GSH, and the transient decrease in GSH which resulted could lead to inhibition of mitosis. While other reports (Nath and Rebhun, '76; Oliver et al., '76) have shown that reagents which oxidize GSH disrupt microtubule-related events, our results showed that such inhibition could be caused by decreased GSH levels alone. 相似文献
8.
9.
10.