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Maurizio Sar Salvatore Bondì Ana Bermejo Mathieu Bourgeois Mathias Bouzin Javier Bustamante Javier de la Puente Angelos Evangelidis Annagrazia Frassanito Egidio Fulco Giuseppe Giglio Gradimir Gradev Matteo Griggio Lina Lpez‐Ricaurte Panagiotis Kordopatis Simeon Marin Juan Martínez Rosario Mascara Ugo Mellone Stefania C. Pellegrino Philippe Pilard Stefano Podofillini Marta Romero Marco Gustin Nicolas Saulnier Lorenzo Serra Athanassios Sfougaris Vicente Urios Matteo Visceglia Konstantinos Vlachopoulos Laura Zanca Jacopo G. Cecere Diego Rubolini 《Journal of Biogeography》2019,46(12):2663-2677
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Banzi M Aguiari G Trimi V Mangolini A Pinton P Witzgall R Rizzuto R del Senno L 《Biochemical and biophysical research communications》2006,350(2):257-262
Polycystin-1 (PC1), the PKD1 gene product, is a membrane receptor which regulates many cell functions, including cell proliferation and apoptosis, both typically increased in cyst lining cells in autosomal dominant polycystic kidney disease. Here we show that PC1 upregulates the NF-kappaB signalling pathway in kidney cells to prevent cell death. Human embryonic kidney cell lines (HEK293(CTT)), stably expressing a PC1 cytoplasmic terminal tail (CTT), presented increased NF-kappaB nuclear levels and NF-kappaB-mediated luciferase promoter activity. This, consistently, was reduced in HEK293 cells in which the endogenous PC1 was depleted by RNA interference. CTT-dependent NF-kappaB promoter activation was mediated by PKCalpha because it was blocked by its specific inhibitor Ro-320432. Furthermore, it was observed that apoptosis, which was increased in PC1-depleted cells, was reduced in HEK293(CTT) cells and in porcine kidney LtTA cells expressing a doxycycline-regulated CTT. Staurosporine, a PKC inhibitor, and parthenolide, a NF-kappaB inhibitor, significantly reduced the CTT-dependent antiapoptotic effect. These data reveal, therefore, a novel pathway by which polycystin-1 activates a PKCalpha-mediated NF-kappaB signalling and cell survival. 相似文献
997.
Balagué C Stürtz N Rey R De Ruiz CS Nader-Macías ME Duffard R De Duffard AM 《FEMS immunology and medical microbiology》2006,48(3):337-346
Clofibric acid (CL) is a compound used to control hypertriglyceridemia, and ethacrynic acid (ET) is administered to enhance diuresis. These compounds are structurally analogous to the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D), as they have a chlorinated phenoxy moiety. As these agents are mainly excreted by the renal route, they could potentially coexist with Escherichia coli in the urinary tract of infected patients. Induction of the in vitro resistance of E. coli to hydrophilic antibiotics was determined by increasing the values of the minimum inhibitory concentration (2-40-fold). These results correlated with drastically inhibited expression of the hydrophilic bacterial channel OmpF. In vivo assays were performed in ascending urinary tract infection in female BALB/c mice. Treatment with the hydrophilic antibiotic cephalexin 25 mg kg(-1) day(-1) by the oral route diminished renal infection. The CFU mean values in the kidneys were between 75% and 89% lower than those in animals without treatment. Simultaneous exposure to CL (at a therapeutic dose, 28.6 mg kg(-1) day(-1)) did not change the effect of the treatment. In contrast, ET at 2.9 mg kg(-1) day(-1) or 2,4-D at 70 mg kg(-1) day(-1) inhibited the antibiotic therapeutic effect. Moreover, 2,4-D dramatically increased bacterial infection after 9 days of exposure. 相似文献
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Alonso De Diego SA Gutiérrez-Rodríguez M Pérez de Vega MJ Casabona D Cativiela C González-Muñiz R Herranz R Cenarruzabeitia E Frechilla D Del Río J Jimeno ML García-López MT 《Bioorganic & medicinal chemistry letters》2006,16(5):1392-1396
A suitable solid-phase approach, based on Fmoc/(t)Bu methodology and on the use of 2-chlorotrityl resin, allowed a rapid and efficient preparation of new GPE analogues. Most of the synthesized tripeptides displayed glutamate receptor binding affinity comparable to that of GPE, but only a few derivatives showed significant neuroprotective activity. 相似文献
999.
Sun C Aspland SE Ballatore C Castillo R Smith AB Castellino AJ 《Bioorganic & medicinal chemistry letters》2006,16(1):104-107
The design, synthesis, and evaluation of two N-alkylmaleimide aldehydes have been achieved, which upon reductive alkylation with the C3'-amino group of doxorubicin (DOX) permits the preparation of DOX conjugates via Michael addition of thiol-containing vectors. This method enables the mild, facile, and high-throughput preparation of DOX conjugates that retain the basic C3'-nitrogen, a pre-requisite for topoisomerase II inhibition. Seven DOX-amino acid conjugates were prepared, each displaying similar inhibitory activity as the parent drug. 相似文献
1000.
Lin X Murray JM Rico AC Wang MX Chu DT Zhou Y Del Rosario M Kaufman S Ma S Fang E Crawford K Jefferson AB 《Bioorganic & medicinal chemistry letters》2006,16(16):4163-4168
A series of 2-pyrimidyl-5-amidothiophenes has been synthesized and evaluated for AKT inhibition. SAR studies resulted in potent inhibitors of AKT with IC(50) values as low as single digit nanomolar as represented by compound 2aa. Compound 2aa showed cellular activity including antiproliferation and downstream target modulation. Selectivity profile is described. A co-crystal of 2aa with PKA is determined and discussed. 相似文献