全文获取类型
收费全文 | 859894篇 |
免费 | 95193篇 |
国内免费 | 1687篇 |
专业分类
956774篇 |
出版年
2018年 | 8504篇 |
2017年 | 8112篇 |
2016年 | 11198篇 |
2015年 | 14477篇 |
2014年 | 17176篇 |
2013年 | 24788篇 |
2012年 | 27605篇 |
2011年 | 27913篇 |
2010年 | 18749篇 |
2009年 | 17380篇 |
2008年 | 24456篇 |
2007年 | 25074篇 |
2006年 | 23518篇 |
2005年 | 22408篇 |
2004年 | 22125篇 |
2003年 | 21083篇 |
2002年 | 20496篇 |
2001年 | 41092篇 |
2000年 | 41046篇 |
1999年 | 32635篇 |
1998年 | 11003篇 |
1997年 | 11671篇 |
1996年 | 10985篇 |
1995年 | 10049篇 |
1994年 | 9947篇 |
1993年 | 9785篇 |
1992年 | 26472篇 |
1991年 | 25340篇 |
1990年 | 24833篇 |
1989年 | 24354篇 |
1988年 | 22370篇 |
1987年 | 21072篇 |
1986年 | 19619篇 |
1985年 | 19559篇 |
1984年 | 15912篇 |
1983年 | 13638篇 |
1982年 | 10310篇 |
1981年 | 9160篇 |
1980年 | 8813篇 |
1979年 | 15039篇 |
1978年 | 11636篇 |
1977年 | 10591篇 |
1976年 | 9850篇 |
1975年 | 10812篇 |
1974年 | 11545篇 |
1973年 | 11308篇 |
1972年 | 10342篇 |
1971年 | 9286篇 |
1970年 | 8112篇 |
1969年 | 7557篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
31.
P Delafontaine K K Griendling M A Gimbrone R W Alexander 《The Journal of biological chemistry》1987,262(30):14549-14554
Potassium depletion decreases blood pressure in vivo and blunts the pressor response to angiotensin II (ang II) without down-regulating the receptor. In cultured rat aortic smooth muscle cells, the ang II-induced signaling sequence is biphasic with rapid hydrolysis of the polyphosphoinositides producing an early (15 s) diacylglycerol (DG) peak and a transient rise in inositol trisphosphate (IP3) and more delayed phosphatidylinositol (PI) hydrolysis resulting in sustained DG formation (peak at 5 min). Exposure of intact vascular smooth muscle cells to low potassium growth medium for 24 h or acutely potassium-depleting cells with nigericin causes selective, marked inhibition of late DG formation (5-min peak inhibited by 60 +/- 8% and 84 +/- 7%, respectively). The early cell response, namely polyphosphoinositide hydrolysis, inositol bis- and trisphosphate production and the 15-s DG peak, is not affected. Analysis of 125I-ang II-binding data reveals no significant differences in either receptor number or binding affinity (Kd) in potassium-depleted cells. Together with its marked inhibitory effect on sustained ang II-induced DG formation, acute potassium depletion effectively blocks internalization of 125I-ang II: there is no significant internalization of the ligand after 5 min at 37 degrees C versus 64 +/- 7% internalization in control cells. Thus, potassium depletion does not alter ang II binding or initial membrane signaling in rat aortic smooth muscle but blocks ligand internalization and selectively and markedly inhibits the development of direct PI hydrolysis and sustained diacylglycerol formation. These findings suggest a role for ligand-receptor processing in generating the sustained cell response and potentially explain the lower blood pressure and decreased pressor response to ang II seen in hypokalemic states in vivo. Furthermore, the ability of K+ depletion to alter secondary signal generation may provide insight into the mechanisms underlying the K+ dependence of a variety of cell functions. 相似文献
32.
Y Tani I Ohkubo S Higashiyama M Kunimatsu M Sasaki 《Comparative biochemistry and physiology. B, Comparative biochemistry》1987,88(2):429-441
1. High mol. wt kininogen (HMW kininogen) was purified to a homogeneous state from porcine plasma. 2. The protein exhibited a strong inhibitory activity for thiol proteinases such as ficin, papain and calpain I, whereas it did not inhibit serine proteinases, trypsin and chymotrypsin. 3. The mol. wt, isoelectric point, amino acid and carbohydrate compositions, stabilities to temperature and pH, kinetic constants, and immunological properties of the porcine HMW kininogen were determined and compared with those of human HMW kininogen. 相似文献
33.
34.
S Kh Khaduev O S Zhukova Ia V Dobrynin K Soda T T Berezov 《Biulleten' eksperimental'no? biologii i meditsiny》1986,101(5):603-604
L-lysine-alpha-oxidase, a new fungal enzyme catalyzing oxidative deamination of L-lysine, exerts an inhibitory effect on DNA, RNA and protein synthesis in human cells of carcinoma ovarius (CaOv) in vitro. 相似文献
35.
36.
P C de Visser N M A J Kriek P A V van Hooft A Van Schepdael D V Filippov G A van der Marel H S Overkleeft J H van Boom D Noort 《The journal of peptide research》2003,61(6):298-306
As part of a program towards the development of novel antibiotics, a convenient method for solid-phase synthesis of the cyclic cationic peptide polymyxin B1 and analogues thereof is described. The methodology, based on cleavage-by-cyclization using Kenner's safety-catch linker, yields crude products with purities ranging from 37-67%. Antibacterial assays revealed that analogues 23-26, in which the (S)-6-methyloctanoic acid moiety is replaced with shorter acyl chains, exhibit distinct antimicrobial activity. The results suggest that the length of the acyl chain is rather critical for antimicrobial activity. On the other hand, substitution of the hydrophobic ring-segment D-Phe-6/Leu-7 in polymyxin B1 with dipeptide mimics (i.e. analogues 27-33) resulted in almost complete loss of antimicrobial activity. 相似文献
37.
38.
Elevated levels of intracellular calcium are a major cause of myocardial dysfunction. To find possible mediators of the deregulated calcium we searched for EF-hand calcium-binding proteins of the S100 family. By PCR technology we identified three members of the S100 protein family (S100 alpha, CACY, and CAPL) in the human heart. We cloned the corresponding cDNAs and examined their expression levels in various human tissues by Northern blot analysis. All three proteins are expressed at high levels in the human heart. Whereas CACY and CAPL mRNAs are expressed ubiquitously, S100 alpha mRNA is restricted to heart, skeletal muscle, and brain. Interestingly, the expression pattern of S100 alpha, CACY, and CAPL in human tissues differs significantly from that in rodent tissues. 相似文献
39.
Localization of cathepsin D in rat liver. Immunocytochemical study using post-embedding immunoenzyme and protein A-gold techniques 总被引:1,自引:0,他引:1
Light and electron microscopic localization of cathepsin D in rat liver was investigated by post-embedding immunoenzyme and protein A-gold techniques. By light microscopy, cytoplasmic granules of parenchymal cells and Kupffer cells were stained for cathepsin D. Weak staining was also noted in sinusoidal endothelial cells. In the parenchymal cells many of positive granules located around bile canaliculi. In the Kupffer cells and the endothelial cells, diffuse staining was noted in the cytoplasm in addition to granular staining. By electron microscopy, gold particles representing the antigenic sites for cathepsin D were seen in typical secondary lysosomes and some multivesicular bodies of the parenchymal cells and Kupffer cells. The lysosomes of the endothelial cells and fat-storing cells were weakly labeled. Quantitative analysis of the labeling density in the lysosomes of these three types of cells demonstrated that the lysosomes of parenchymal cells and Kupffer cells are main containers of cathepsin D in rat liver. The results suggest that cathepsin D functions in the intracellular digestive system of parenchymal cells and Kupffer cells but not so much in that of the endothelial cells. 相似文献
40.
R. A. Mueller M. J. Rosner J. N. Ghia S. K. Powers E. R. Kafer R. D. Hunt 《Cellular and molecular neurobiology》1988,8(2):235-243
1. Examination of the cerebrospinal fluid (CSF) of head-injured patients reveals that the concentration of intraventricular xanthine is elevated and that of uridine is decreased relative to those of adult lumbar CSF. 2. No correlations were observed between CSF lactate and CSF hypoxanthine, xanthine, or uridine, suggesting that changes in purine metabolites and the pyrimidine nucleoside do not index similar cellular events as does lactic acid production. 3. Ventricular CSF from hydrocephalic infants had uridine and hypoxanthine concentrations not significantly different from those of normal adult lumbar CSF, but xanthine was significantly elevated. 4. Since uridine has anticonvulsant properties and is a crucial substrate for cerebral metabolism, it may be useful to evaluate this pyrimidine for use in the management of patients with head injury. 相似文献