全文获取类型
收费全文 | 707篇 |
免费 | 59篇 |
国内免费 | 2篇 |
专业分类
768篇 |
出版年
2024年 | 4篇 |
2023年 | 11篇 |
2022年 | 21篇 |
2021年 | 29篇 |
2020年 | 25篇 |
2019年 | 27篇 |
2018年 | 38篇 |
2017年 | 20篇 |
2016年 | 28篇 |
2015年 | 33篇 |
2014年 | 49篇 |
2013年 | 38篇 |
2012年 | 49篇 |
2011年 | 66篇 |
2010年 | 29篇 |
2009年 | 29篇 |
2008年 | 26篇 |
2007年 | 18篇 |
2006年 | 19篇 |
2005年 | 18篇 |
2004年 | 20篇 |
2003年 | 17篇 |
2002年 | 19篇 |
2001年 | 10篇 |
2000年 | 8篇 |
1999年 | 6篇 |
1998年 | 3篇 |
1996年 | 5篇 |
1995年 | 8篇 |
1994年 | 5篇 |
1992年 | 5篇 |
1987年 | 3篇 |
1986年 | 3篇 |
1985年 | 5篇 |
1984年 | 5篇 |
1982年 | 2篇 |
1981年 | 4篇 |
1979年 | 5篇 |
1978年 | 5篇 |
1976年 | 4篇 |
1975年 | 6篇 |
1974年 | 3篇 |
1973年 | 2篇 |
1972年 | 3篇 |
1971年 | 2篇 |
1969年 | 4篇 |
1968年 | 2篇 |
1967年 | 4篇 |
1965年 | 4篇 |
1964年 | 2篇 |
排序方式: 共有768条查询结果,搜索用时 15 毫秒
31.
Jacques D Abdel Malak NA Sader S Perreault C 《Canadian journal of physiology and pharmacology》2003,81(3):259-266
The aims of the present study are to investigate the presence and distribution of angiotensin II (Ang II), as well as AT1 and AT2 receptors, in endocardial endothelial cells (EECs) and to determine if the effect of Ang II on intracellular calcium in these cells is mediated via the AT1 or the AT2 receptor. Immunofluorescence and 3D confocal microscopy techniques were used on 20-week-old fetal human EECs. Our results showed that Ang II and its receptors, the AT1 and the AT2 types, are present and exhibit a different distribution in human EECs. Ang II labelling is found throughout the cell with a fluorescence signal higher in the cytosol when compared with the nucleus. Like Ang II, the AT1 receptor fluorescence signal is also homogeneously distributed in human EECs but with a preferential labelling at the level of the nucleus, while the AT2 receptor labelling is solely present in the nucleus. Using fluo-3 and 3D confocal microscopy technique, superfusion of human EECs with increasing concentration of Ang II induced a dose-dependent sustained increase in free cytosolic and nuclear Ca2+ levels. This effect of Ang II on human EEC's intracellular Ca2+ ([Ca2+]) was completely prevented by losartan, an AT1 receptor antagonist. Our results suggest that Ang II, as well as AT1 and AT2 receptors, is present but differentially distributed in EECs of 20-week-old fetal human hearts, and that the AT1 receptor mediates the effects of Ang II on [Ca2+]i in these cells. 相似文献
32.
El-hamid Ismail A Abdel Aleem AA Abdel Bary H El-Assaly S 《Nucleosides, nucleotides & nucleic acids》2002,21(6-7):469-475
2-Naphthylsulfonylhydrazine was reacted with aromatic aldehydes or aldehydo sugars to give the corresponding hydrazones which undergo Michael addition reactions with malononitrile or ethyl cyanoacetate to form pyrazole derivatives. 相似文献
33.
Red blood cells (RBCs) are probably the most common target through the damaging action of reactive oxygen species on the cells. The photohemolysis activity of m-chloroperbenzoic acid (CPBA) was concentration- and exposure time-dependent. Twenty minutes photo exposure time and 200 μm of CPBA concentration were optimum to study the effect of generated superoxide (O2-) and hydroxyl (&bull•OH) radicals on RBCs. RBCs lysis photosensitized by CPBA was investigated in the presence of [(VL2O)(VL2H2O)]Cl6, [MnL2O]2Cl42H2O, [FeL2Cl2]Cl H2O, [CoL2Cl2]4H2O or [ZnL2Cl2]H2O respectively, where L is 2-methylaminopyridine, with SOD-mimetic activities with the aim of ascertaining their protective activity towards the photo induced cell damage. The decrease of photolytic activity caused by these complexes was concentration-dependent and the maximum percentage of protective activity was 75, 70, 68, 57 or 24% for [(VL2O)(VL2H2O)]Cl6, [MnL2O]2Cl4 2H2O, [FeL2Cl2]Cl H2O, [CoL2Cl2]4H2O or [ZnL2Cl2]H2O complex respectively, against the cell irradiated without addition of metal complexes. The comparison between the decrease of photolytic activity caused by these complexes and their SOD-mimetic activity of these metal complexes showed an appreciable correlation. 相似文献
34.
The 1-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-3-aryl-5-benzyl (or substituted benzyl)-1,2,4-triazin-6(1H)-/ones or thiones were prepared via galactosidation of 3-aryl-5-benzyl (or substituted benzyl)-1,2,4-triazin-6(1H)-/ones or thiones with 2,3,4,6-tetra-O-acetyl-alpha-D-galactopyranosyl bromide. The structure of the new galactosyl derivatives was based on both spectroscopic and chemical evidences. 相似文献
35.
Synthetic routes towards different 2-alpha-L-arabinopyranosyl-3-thioxo-2,3-dihydro-1,2,4-triazin-5(4H)-/ones or thiones were investigated. Primary human anticancer screening of two selected compounds resulted in an active compound against SF-268 (CNS) cell line. 相似文献
36.
The tyrosine kinase p72(Syk) plays a critical role in platelet signal transduction. It associates with the platelet receptor for the Fc domain of IgGs, FcgammaRII, following stimulation by FcgammaRII cross-linking. Here, we show that p72(Syk) and FcgammaRII tyrosine phosphorylation and association occured following platelet stimulation by: (1) two monoclonal antibodies, which form a bridge between a target antigen and FcgammaRII, and (2) the G-protein-coupled receptor agonist thrombin. The kinetics of the p72(Syk)/FcgammaRII association depended on the signalling pathway (i.e., the antigen targeted or the thrombin receptor). We established a direct relationship between the level of FcgammaRII phosphorylation and the detection of its association with p72(Syk). Inhibition of p72(Syk) by piceatannol resulted in partial or total inhibition of FcgammaRII phosphorylation, after immunological activation or addition of thrombin, respectively, suggesting that p72(Syk) participates in FcgammaRII phosphorylation. The results provide evidence that p72(Syk)/FcgammaRII association is not restricted to immunological activation. 相似文献
37.
Four new triterpenoid saponins were isolated and identified from the aerial parts of Fagonia cretica. They were characterized as 3-O-[beta-D-glucopyranosyl (1-->2)-alpha-L-arabinopyranosyl] hederagenin 28-O-beta-D-glucopyranosyl ester, 3-O-[beta-D-glucopyranosyl (1-->2)-alpha-L-arabinopyranosyl] oleanolic acid 28-O-[beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranosyl] ester, 3-O-[beta-D-glucopyranosyl (1-->2)-alpha-L-arabinopyranosyl] 27-hydroxy oleanolic acid 28-O-[beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranosyl] ester and 3beta-O-[beta-D-glucopyranosyl (1-->2)-alpha-L-arabinopyranosyl] olean-12-en-27-al-28-oic acid 28-O-[beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranosyl] ester. The structures of the saponins were assigned by spectral analyses (FABMS, 1H, 13C NMR, 1H-1H COSY, TOCSY, HMQC and HMBC spectra) and NOE experiments. To the best of our knowledge the genin 3beta hydroxy olean-12-en-27-al-28-oic acid is new. 相似文献
38.
Abdel Monim El-Mofty George R. Mikhail Mohamed M. Nada Maher Kamel Moawad 《Mycopathologia》1969,37(3):257-262
Summary A selected group of 525 individuals with pulmonary diseases, granulomas and other medical conditions was tested for histoplasmin and blastomycin dermal reactions. No positive results were observed. Few doubtful positive reactions were recorded (3 to histoplasmin and 7 to blastomycin). None of the patients with chronic cutaneous granulomas exhibited any reaction.Although the number of subjects studied is small, these preliminry findings suggest the probable absence of histoplasmosis and blastomycosis in Egypt. 相似文献
39.
Yara Rhayem Catherine Le Stunff Waed Abdel Khalek Colette Auzan Jerome Bertherat Agnès Linglart Alain Couvineau Caroline Silve Eric Clauser 《The Journal of biological chemistry》2015,290(46):27816-27828
The main target of cAMP is PKA, the main regulatory subunit of which (PRKAR1A) presents mutations in two genetic disorders: acrodysostosis and Carney complex. In addition to the initial recurrent mutation (R368X) of the PRKAR1A gene, several missense and nonsense mutations have been observed recently in acrodysostosis with hormonal resistance. These mutations are located in one of the two cAMP-binding domains of the protein, and their functional characterization is presented here. Expression of each of the PRKAR1A mutants results in a reduction of forskolin-induced PKA activation (measured by a reporter assay) and an impaired ability of cAMP to dissociate PRKAR1A from the catalytic PKA subunits by BRET assay. Modeling studies and sensitivity to cAMP analogs specific for domain A (8-piperidinoadenosine 3′,5′-cyclic monophosphate) or domain B (8-(6-aminohexyl)aminoadenosine-3′,5′-cyclic monophosphate) indicate that the mutations impair cAMP binding locally in the domain containing the mutation. Interestingly, two of these mutations affect amino acids for which alternative amino acid substitutions have been reported to cause the Carney complex phenotype. To decipher the molecular mechanism through which homologous substitutions can produce such strikingly different clinical phenotypes, we studied these mutations using the same approaches. Interestingly, the Carney mutants also demonstrated resistance to cAMP, but they expressed additional functional defects, including accelerated PRKAR1A protein degradation. These data demonstrate that a cAMP binding defect is the common molecular mechanism for resistance of PKA activation in acrodysosotosis and that several distinct mechanisms lead to constitutive PKA activation in Carney complex. 相似文献
40.
Tabrizi MA Baraldi PG Preti D Romagnoli R Saponaro G Baraldi S Moorman AR Zaid AN Varani K Borea PA 《Bioorganic & medicinal chemistry》2008,16(5):2419-2430
A new series of 1,3-dipropyl-8-(1-phenylacetamide-1H-pyrazol-3-yl)-xanthine derivatives has been identified as potent A(2B) adenosine receptor antagonists. The products have been evaluated for their binding affinities for the human A(2B), A(1), A(2A), and A(3) adenosine receptors. N-(4-chloro-phenyl)-2-[3-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-5-methyl-pyrazol-1-yl] (11c) showed a high affinity for the human A(2B) adenosine receptor K(i)=7nM and good selectivity (A(1), A(2A), A(3)/A(2B)>140). Synthesis and SAR of this novel class of compounds is presented herein. 相似文献