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91.
Chia-Chun Yu Shih-Ping Liu Jui-Ling Hsu John TA Hsu Konstantin V Kudryavtsev Jih-Hwa Guh 《Journal of biomedical science》2015,22(1)
Background
Hormone-refractory prostate cancer (HRPC), which is resistant to hormone therapy, is a major obstacle in clinical treatment. An approach to inhibit HRPC growth and ultimately to kill cancers is highly demanded.Results
KUD773 induced the anti-proliferative effect and subsequent apoptosis in PC-3 and DU-145 (two HRPC cell lines); whereas, it showed less active in normal prostate cells. Further examination showed that KUD773 inhibited tubulin polymerization and induced an increase of mitotic phosphoproteins and polo-like kinase 1 (PLK1) phosphorylation, indicating a mitotic arrest of the cell cycle through an anti-tubulin action. The kinase assay demonstrated that KUD773 inhibited Aurora A activity. KUD773 induced an increase of Cdk1 phosphorylation at Thr161 (a stimulatory phosphorylation site) and a decrease of phosphorylation at Tyr15 (an inhibitory phosphorylation site), suggesting the activation of Cdk1. The data were substantiated by an up-regulation of cyclin B1 (a Cdk1 partner). Furthermore, KUD773 induced the phosphorylation and subsequent down-regulation of Bcl-2 and activation of caspase cascades.Conclusions
The data suggest that KUD773 induces apoptotic signaling in a sequential manner. It inhibits tubulin polymerization associated with an anti-Aurora A activity, leading to Cdk1 activation and mitotic arrest of the cell cycle that in turn induces Bcl-2 degradation and a subsequent caspase activation in HRPCs. 相似文献92.
Singh RK Mandal T Balsubramanian N Viaene T Leedahl T Sule N Cook G Srivastava DK 《Bioorganic & medicinal chemistry letters》2011,21(19):5920-5923
We report, for the first time, that certain N-acetylthiourea derivatives serve as highly potent and isozyme selective activators for the recombinant form of human histone deacetylase-8 in the assay system containing Fluor-de-Lys as a fluorescent substrate. The experimental data reveals that such activating feature is manifested via decrease in the K(m) value of the enzyme's substrate and increase in the catalytic turnover rate of the enzyme. 相似文献
93.
Savall BM Gomez L Chavez F Curtis M Meduna SP Kearney A Dunford P Cowden J Thurmond RL Grice C Edwards JP 《Bioorganic & medicinal chemistry letters》2011,21(21):6577-6581
This report discloses the development of a series of tricyclic histamine H(4) receptor antagonists. Starting with a low nanomolar benzofuranopyrimidine HTS hit devoid of pharmaceutically acceptable properties, we navigated issues with metabolism and solubility to furnish a potent, stable and water soluble tricyclic histamine H(4) receptor antagonist with desirable physiochemical parameters which demonstrated efficacy a mouse ova model. 相似文献
94.
Nagarapu L Mateti J Gaikwad HK Bantu R Sheeba Rani M Prameela Subhashini NJ 《Bioorganic & medicinal chemistry letters》2011,21(14):4138-4140
A new series of 3-phenyl-N-[3-(4-phenylpiperazin-1yl)propyl]-1H-pyrazole-5-carboxamide derivatives were synthesized and investigated their anti-inflammatory activities using carrageenan-induced rat paw edema model in vivo. All the synthesized compounds were found to be potent anti-inflammatory agents. 相似文献
95.
Bello C Dal Bello G Cea M Nahimana A Aubry D Garuti A Motta G Moran E Fruscione F Pronzato P Grossi F Patrone F Ballestrero A Dupuis M Sordat B Zimmermann K Loretan J Wartmann M Duchosal MA Nencioni A Vogel P 《Bioorganic & medicinal chemistry》2011,19(24):7720-7727
New derivatives of 1,4-dideoxy-1,4-imino-d-ribitol have been prepared and evaluated for their cytotoxicity on solid and haematological malignancies. 1,4-Dideoxy-5-O-[(9Z)-octadec-9-en-1-yl]-1,4-imino-d-ribitol (13, IC50 ∼2 μM) and its C18-analogues (IC50 <10 μM) are cytotoxic toward SKBR3 (breast cancer) cells. 13 also inhibits (IC50 ∼8 μM) growth of JURKAT cells. 相似文献
96.
97.
Ferdinand Bohlmann Thomas Gerke Jasmin Jakupovic Robert M. King Harold Robinson 《Phytochemistry》1984,23(5):1183-1184
Viguiera oblongifolia afforded two known furanoheliangolides and a new cadinane derivative whose structure was established by spectroscopic methods. From V. lanceolata 17,18-dihydrobudlein A was isolated. 相似文献
98.
PML5 is a functional derivative of a family I.3 lipase from Pseudomonas sp. MIS38 and contains five repeats of a nine-residue sequence motif. Two aspartate residues within the second and third repetitive sequences of PML5 were replaced by Ala. The secretion level, intracellular accumulation level, and stability of the resultant mutant protein were greatly reduced as compared to those of PML5. In addition, this mutant protein was inactive and did not bind Ca2+ ion. We propose that the repetitive sequences of PML5 form a beta-roll structure in the cells and thereby contribute to the intracellular stability and secretion efficiency of the protein. 相似文献
99.
Sergio Oddi Filomena Fezza Giuseppina Catanzaro Chiara De Simone Mariangela Pucci Daniele Piomelli Alessandro Finazzi-Agrò Mauro Maccarrone 《Journal of lipid research》2010,51(8):2435-2444
Nonspecific binding of anandamide to plastic exhibits many features that could be mistaken as biological processes, thereby representing an important source of conflicting data on the uptake and release of this lipophilic substance. Herein, we propose an improved method to assay anandamide transport, by using glass slides (i.e., coverslips) as physical support to grow cells. Although the results obtained using plastic do not differ significantly from those obtained using glass, the new procedure has the advantage of being faster, simpler, and more accurate. In fact, the lack of aspecific adsorption of anandamide to the glass surface yields a lower background and a higher precision and accuracy in determining transport kinetics, especially for the export process. Remarkably, the kinetic parameters of anandamide uptake obtained with the old and the new procedures may be similar or different depending on the cell type, thus demonstrating the complexity of the interference of plastic on the transport process. In addition, the novel procedure is particularly suitable for visualization and measurement of anandamide transport in intact cells by using a biotinylated derivative in confocal fluorescence microscopy. 相似文献
100.
Coumarin-based triazoles were synthesized from 3-azidomethylcoumarin and a terminal acetylenic compound. Uncatalysed thermal conditions result in a mixture of both 1,4- and 1,5-regioisomers or the thermodynamically more stable 1,4-regioisomer, whereas the Cu(I)-catalysed reaction affords only the favourable 1,4-regioisomer. B3LYP/6-31G(d) level of theory has been used to calculate geometry and frequency features of the reactants, transition states (TSs) and products. Computational studies further reveal that 1,4-regioisomeric products are more favourable and also thermodynamically more stable compared to the 1,5-regioisomers. 相似文献