全文获取类型
收费全文 | 217篇 |
免费 | 26篇 |
出版年
2023年 | 1篇 |
2022年 | 4篇 |
2021年 | 5篇 |
2020年 | 6篇 |
2019年 | 9篇 |
2018年 | 7篇 |
2017年 | 6篇 |
2016年 | 4篇 |
2015年 | 6篇 |
2014年 | 16篇 |
2013年 | 14篇 |
2012年 | 17篇 |
2011年 | 14篇 |
2010年 | 12篇 |
2009年 | 17篇 |
2008年 | 9篇 |
2007年 | 12篇 |
2006年 | 16篇 |
2005年 | 14篇 |
2004年 | 9篇 |
2003年 | 8篇 |
2002年 | 11篇 |
2001年 | 3篇 |
2000年 | 2篇 |
1999年 | 2篇 |
1998年 | 2篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1992年 | 2篇 |
1989年 | 1篇 |
1986年 | 1篇 |
1978年 | 1篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1971年 | 2篇 |
1969年 | 1篇 |
排序方式: 共有243条查询结果,搜索用时 15 毫秒
211.
212.
Marisol Vieites Lucía Otero Oscar E. Piro Carlos Mauricio R. Sant’ Anna Eliezer J. Barreiro Dinorah Gambino 《Inorganica chimica acta》2005,358(11):3065-3074
ortho-Hydroxybenzaldehyde semicarbazone (salicylaldehyde semicarbazone) undergoes chemo-selective hydrolysis of the iminic carbon nitrogen double bond through its reaction with [RuCl2(dmso)4] in ethanol in the presence of water, yielding free salicylaldehyde and semicarbazide that remains coordinated to the ruthenium ion as a bidentate N,O-donor to afford [RuCl2(dmso)2(semicarbazide)] · 2H2O complex. The ruthenium-semicarbazide complex has been characterized by 1H NMR and FTIR spectroscopies and X-ray diffraction methods. Related semicarbazones, derived from p-hydroxybenzaldehyde and benzaldehyde, were not hydrolyzed under the same conditions, suggesting a significant role of the structural o-hydroxy motive in the reaction. Theoretical studies were performed in order to gain further insight on the mechanism of reaction. Results support the hypothesis that the ortho-hydroxy moiety, in the keto tautomeric form, participates in the chemo-selective hydrolysis promoted by [RuCl2(dmso)4]. 相似文献
213.
Penela P Ribas C Aymerich I Eijkelkamp N Barreiro O Heijnen CJ Kavelaars A Sánchez-Madrid F Mayor F 《The EMBO journal》2008,27(8):1206-1218
Cell migration requires integration of signals arising from both the extracellular matrix and messengers acting through G protein-coupled receptors (GPCRs). We find that increased levels of G protein-coupled receptor kinase 2 (GRK2), a key player in GPCR regulation, potentiate migration of epithelial cells towards fibronectin, whereas such process is decreased in embryonic fibroblasts from hemizygous GRK2 mice or upon knockdown of GRK2 expression. Interestingly, the GRK2 effect on fibronectin-mediated cell migration involves the paracrine/autocrine activation of a sphingosine-1-phosphate (S1P) Gi-coupled GPCR. GRK2 positively modulates the activity of the Rac/PAK/MEK/ERK pathway in response to adhesion and S1P by a mechanism involving the phosphorylation-dependent, dynamic interaction of GRK2 with GIT1, a key scaffolding protein in cell migration processes. Furthermore, decreased GRK2 levels in hemizygous mice result in delayed wound healing rate in vivo, consistent with a physiological role of GRK2 as a regulator of coordinated integrin and GPCR-directed epithelial cell migration. 相似文献
214.
Elena Barreiro María D. Couce Angeles Sánchez-González José M. Varela 《Journal of inorganic biochemistry》2010,104(5):551-2359
Compounds of the type [(AuPPh3)2(xspa)]; H2xspa [x:p = 3-phenyl-, f = 3-(2-furyl)-, t = 3-(2-thienyl)-, -o-py = 3-(2-pyridyl)-, Clp = 3-(2-chlorophenyl)-, -o-mp = 3-(2-methoxyphenyl)-, -p-mp = 3-(4-methoxyphenyl)-, -o-hp = 3-(2-hydroxyphenyl)-, -p-hp = 3-(4-hydroxyphenyl)-, -diBr-o-hp = 3-(3,5-dibromo-2-hydroxyphenyl)-; spa = 2-sulfanyl propenoato] were synthesized and characterized by IR and NMR (1H, 13C and 31P) spectroscopy and by FAB mass spectrometry. The structures of [(AuPPh3)2(Clpspa)], [(AuPPh3)2(o-hpspa)], [(AuPPh3)2(p-hpspa)]·MeOH and [(AuPPh3)2(diBr-o-hpspa)]·2Me2CO show the dinuclear nature of the complexes with the two gold atoms, one of which is also O-bonded to an O atom of the carboxylate group, bonded to the S atom. The in vitro antitumor activities against the HeLa-229, A2780 and A2780cis cell lines were determined and the compounds were found to be highly effective, in particular against the A2780cis cell line, with eight of the nine compounds having IC50 values better than that of cisplatin. This behavior is indicative of a high ability to circumvent the cellular resistance to this drug. 相似文献
215.
Sperandio da Silva GM Lima LM Fraga CA Sant'Anna CM Barreiro EJ 《Bioorganic & medicinal chemistry letters》2005,15(15):3506-3509
In this work, we present the results of two combined approaches, molecular docking and comparative molecular field analysis (CoMFA), to propose how the selective cyclooxygenase-2 inhibitor celecoxib could act as a p38 mitogen-activated protein (MAP) kinase inhibitor. The docking analysis revealed why celecoxib has a less favorable binding energy (DeltaG= -12.4kcal/mol) than the selective p38 MAP kinase (p38 MAPK) inhibitor, SB203580 (DeltaG= -22.2kcal/mol). The CoMFA results revealed unfavorable steric effects that can be related to the predicted lower p38 MAP kinase inhibitory activity of celecoxib. Additionally, FlexX and CoMFA results also suggested that etoricoxib, another selective COX-2 inhibitor, could inhibit p38 MAP kinase. 相似文献
216.
Machado AL Lima LM Araújo JX Fraga CA Koatz VL Barreiro EJ 《Bioorganic & medicinal chemistry letters》2005,15(4):1169-1172
As part of an ongoing effort to develop new thalidomide analogues as antiinflammatory lead-candidates, this paper describes the synthesis and antiinflammatory activity of novel N-phenyl-phthalimide functionalized derivatives (4a-d, 5a,b, 6a,b). The target compounds were assayed in an acute lung inflammatory model and all compounds were able to inhibit TNF-alpha production and subsequent neutrophil recruitment in the LPS-acute lung inflammatory model. 相似文献
217.
Viegas C Bolzani VS Pimentel LS Castro NG Cabral RF Costa RS Floyd C Rocha MS Young MC Barreiro EJ Fraga CA 《Bioorganic & medicinal chemistry》2005,13(13):4184-4190
Five new piperidine alkaloids were designed from natural (-)-3-O-acetyl-spectaline and (-)-spectaline that were obtained from the flowers of Senna spectabilis (sin. Cassia spectabilis, Leguminosae). Two semi-synthetic analogues (7 and 9) inhibited rat brain acetylcholinesterase, showing IC50 of 7.32 and 15.1 microM, and were 21 and 9.5 times less potent against rat brain butyrylcholinesterase, respectively. Compound 9 (1mg/kg, i.p.) was fully efficacious in reverting scopolamine-induced amnesia in mice. The two active compounds (7 and 9) did not show overt toxic effects at the doses tested in vivo. 相似文献
218.
A proposed molecular basis for the selective resveratrol inhibition of the PGHS-1 peroxidase activity 总被引:1,自引:0,他引:1
Kümmerle AE Sperandio da Silva GM Sant'Anna CM Barreiro EJ Fraga CA 《Bioorganic & medicinal chemistry》2005,13(21):5981-5985
Docking results have enabled us to propose how resveratrol could act as a selective PGHS-1 peroxidase site inhibitor. The docking model has predicted a slightly less favorable DeltaG(bind) (-17.9 kcal/mol) of the resveratrol to the PGHS-2 peroxidase site in comparison with its corresponding binding to the PGHS-1 (-20.4 kcal/mol). The formation of hydrogen bonds among the hydroxyl groups of the resveratrol phenyl rings, the backbone of Fe-heme and the carbonyl group of Leu294 inside the PGHS-1 peroxidase site, associated with the absence of His214 in the backbone of PGHS-1, are essential features that are required to maintain the aromatic rings of the natural product parallel to the Fe-heme group and transverse to the peroxidase access channel promoting a large steric hindrance at this site and its consequent selective inhibition. 相似文献
219.
In this work, we propose a molecular model of the L-type calcium channel pore from the human cardiac alpha1 subunit. Four glutamic acid residues, the EEEE locus, located at highly conserved P loops (also called SS1-SS2 segments) of the alpha1 subunit, molecularly express the calcium channel selectivity. The proposed alpha-helix structure for the SS1 segment, analyzed through molecular dynamics simulations in aqueous-phase, was validated by the plotting of Ramachandran diagrams for the averaged structures and by the analysis of i and i + 4 helical hydrogen bonding between the amino acid residues. The results of the simulation of the calcium channel model with one and two Ca2+ ions at the binding site are in accordance with mutation studies which suggest that the EEEE locus in the L-type calcium channel must form a single high-affinity binding site. These results suggest that the Ca2+ permeation through the channel would be derived from competition between two ions for the only high-affinity binding site. Furthermore, the experimentally observed blocking of the Na+ flux at micromolar Ca2+ concentrations, probably due to the occupancy of the single high-affinity binding site for one Ca2+, was also reproduced by our model. 相似文献
220.
Rey M Vicente-Manzanares M Viedma F Yáñez-Mó M Urzainqui A Barreiro O Vázquez J Sánchez-Madrid F 《Journal of immunology (Baltimore, Md. : 1950)》2002,169(10):5410-5414
The binding of chemokines to their receptors guides lymphocyte migration. However, the precise mechanism that links the chemotactic signals with the energy and traction force generated by the actomyosin complex of the cell has not been elucidated. Using biochemical approaches and mass spectrometry analysis, we found an association between the C-termini of CXCR4 and CCR5 and the motor protein nonmuscle myosin H chain-IIA. Immunoprecipitation experiments revealed that this association also occurs between the endogenous molecules in T lymphocytes. As expected, myosin L chain was also associated with CXCR4. Confocal microscopy analysis showed that CXCR4 and motor protein nonmuscle myosin H chain-IIA colocalize at the leading edge of migrating T lymphocytes, together with filamentous actin and myosin L chain. These results provide the first evidence of a biochemical association between chemokine receptors and motor proteins, a mechanosignaling mechanism that may have a key role in lymphocyte migration. 相似文献