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101.
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The bis(pyrazol-1-yl)azine ligands 2,3-bis(pyrazol-1-yl)quinoxaline (bpzqnx), 2,3-bis(pyrazol-1-yl)pyrazine (bpzprz) and 3,6-bis(3,5-dimethylpyrazol-1-yl)pyridazine (bpz*pdz) were prepared by the reaction of pyrazolate salts and the corresponding azine dichloride derivatives. The reaction of these ligands with Ru(arene) precursors led to the mononuclear complexes [RuCl(arene)(L)]BPh4 (arene = p-cymene, L = bpzqnx, 1, bpzprz, 5, bpz*pdz, 7; arene = C6H6, L = bpzqnx, 2, bpzprz, 6, bpz*pdz, 8) with the N-donor ligand coordinated in a bidentate chelate way. In general, the ligands coordinate through one pyrazole ring and the azine, except in the cases of 1 and 2 where the two pyrazolyl rings are coordinated to the metal in a symmetrical way. When the reactions between the ruthenium precursors and bpzqnx are carried out in MeOH, the complexes [RuCl(arene)(OMepzqnx)]BPh4 with partially methanolyzed ligands are isolated (arene = p-cymene, 3; C6H6, 4). In this process a methoxy group has replaced one of the pyrazole groups in the ligand. The X-ray structures of 6 and 7 have been determined. These compounds have a three-legged piano-stool structure with cations and anions packed through weak interactions. Complexes 1-8 are active in ketone hydrogenation transfer processes even in the absence of base. 相似文献
104.
Mourad Chioua Abdelouahid Samadi Elena Soriano Olivier Lozach Laurent Meijer José Marco-Contelles 《Bioorganic & medicinal chemistry letters》2009,19(16):4566-4569
The synthesis and biological evaluation of a number of differently substituted 3,6-diamino-1H-pyrazolo[3,4-b]pyridine derivatives are reported. From the inhibition results on a selection of disease-relevant protein kinases [IC50 (μM) DYRK1A = 11; CDK5 = 0.41; GSK-3 = 1.5] we have observed that 3,6-diamino-4-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile (4) constitutes a potential new and simple lead compound in the search of drugs for the treatment of Alzheimer’s disease. 相似文献
105.
Indalecio Quesada‐Soriano Lorien J. Parker Alessandra Primavera Juan M. Casas‐Solvas Antonio Vargas‐Berenguel Carmen Barón Craig J. Morton Anna Paola Mazzetti Mario Lo Bello Michael W. Parker Luis García‐Fuentes 《Protein science : a publication of the Protein Society》2009,18(12):2454-2470
The effect of the Y108V mutation of human glutathione S‐transferase P1‐1 (hGST P1‐1) on the binding of the diuretic drug ethacrynic acid (EA) and its glutathione conjugate (EASG) was investigated by calorimetric, spectrofluorimetric, and crystallographic studies. The mutation Tyr 108 → Val resulted in a 3D‐structure very similar to the wild type (wt) enzyme, where both the hydrophobic ligand binding site (H‐site) and glutathione binding site (G‐site) are unchanged except for the mutation itself. However, due to a slight increase in the hydrophobicity of the H‐site, as a consequence of the mutation, an increase in the entropy was observed. The Y108V mutation does not affect the affinity of EASG for the enzyme, which has a higher affinity (Kd ~ 0.5 μM) when compared with those of the parent compounds, K ~ 13 μM, K ~ 25 μM. The EA moiety of the conjugate binds in the H‐site of Y108V mutant in a fashion completely different to those observed in the crystal structures of the EA or EASG wt complex structures. We further demonstrate that the ΔCp values of binding can also be correlated with the potential stacking interactions between ligand and residues located in the binding sites as predicted from crystal structures. Moreover, the mutation does not significantly affect the global stability of the enzyme. Our results demonstrate that calorimetric measurements maybe useful in determining the preference of binding (the binding mode) for a drug to a specific site of the enzyme, even in the absence of structural information. 相似文献
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JF Yuan SJ Zhang O Jafer RA Furlong OE Chausiaux CA Sargent GH Zhang NA Affara 《BMC microbiology》2009,9(1):246
Background
Pseudorabies virus (PRV) is an alphaherpesviruses whose native host is pig. PRV infection mainly causes signs of central nervous system disorder in young pigs, and respiratory system diseases in the adult. 相似文献109.
110.
N.B. Pierangeli S.V. Soriano I. Roccia H.F.J. Bergagna L.E. Lazzarini A. Celescinco A.V. Kossman M.S. Saiz J.A. Basualdo 《Parasitology international》2010,59(3):394-399
Hydatidosis is endemic in Neuquén, Patagonia, Argentina, even though sanitary authorities have been performing a control programme since 1970. At present, the programme is in consolidation phase, and dogs have being evaluated by arecoline purgation. The aims of this study were to evaluate diagnostic performance of a coproantigen (CAg) ELISA test developed “in house” and to assess CAg detection in prepatent period. We examined 8 dogs experimentally infected with Echinococcus granulosus and 403 rural dogs in an endemic area in Neuquén using CAg ELISA test and arecoline purgation. Within the experimental dog group, sensitivity and specificity of the test were 93.6% and 88.5% respectively. In rural dogs group, the overall prevalence of canine echinococcosis was 3.7% using arecoline purgation and 12.4% by the CAg test; sensitivity and specificity of the test using arecoline purge as standard were 73.3% and 89.9% respectively. Possible cross reactions in CAg test were evaluated in rural dogs: CAg was undetectable in 96.4% of the dogs infected only with taeniids non-E. granulosus, and in 90.1% of dogs infected with non-taeniid helminths. The CAg test could detect infections within prepatent period and produced negative results after worm expulsion. Our test showed adequate diagnostic performance with experimentally and naturally infected dogs, in the epidemiological situation of Neuquén. Employment of this sensitive and practical method for surveillance in the control programme in Neuquén would improve screening of canine echinococcosis by detecting infected dogs even with low burdens or within prepatent period. 相似文献