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991.
Ambuj Kumar Vidya Rajendran Rao Sethumadhavan 《Journal of biomolecular structure & dynamics》2013,31(3):394-405
CK1δ (Casein kinase I isoform delta) is a member of CK1 kinase family protein that mediates neurite outgrowth and the function as brain-specific microtubule-associated protein. ATP binding kinase domain of CK1δ is essential for regulating several key cell cycle signal transduction pathways. Mutation in CK1δ protein is reported to cause cancers and affects normal brain development. S97C mutation in kinase domain of CK1δ protein has been involved to induce breast cancer and ductal carcinoma. We performed molecular docking studies to examine the effect of this mutation on its ATP-binding affinity. Further, we conducted molecular dynamics simulations to understand the structural consequences of S97C mutation over the kinase domain of CK1δ protein. Docking results indicated the loss of ATP-binding affinity of mutant structure, which were further rationalized by molecular dynamics simulations, where a notable loss in 3-D conformation of CK1δ kinase domain was observed in mutant as compared to native. Our results explained the underlying molecular mechanism behind the observed cancer associated phenotype caused by S97C mutation in CK1δ protein. 相似文献
992.
Khyati Girdhar Budheswar Dehury Mahender Kumar Singh Vineeth P. Daniel Abhinav Choubey Surbhi Dogra 《Journal of biomolecular structure & dynamics》2013,31(15):3976-3986
AbstractThe glucagon-like peptide-1 receptor (GLP-1R) is a well-known target of therapeutics industries for the treatment of various metabolic diseases like type 2 diabetes and obesity. The structural–functional relationships of small molecule agonists and GLP-1R are yet to be understood. Therefore, an attempt was made on structurally known GLP-1R agonists (Compound 1, Compound 2, Compound A, Compound B, and (S)-8) to study their interaction with the extracellular domain of GLP-1R. In this study, we explored the dynamics, intrinsic stability, and binding mechanisms of these molecules through computational modeling, docking, molecular dynamics (MD) simulations and molecular mechanics Poisson–Boltzmann surface area (MM/PBSA) binding free energy estimation. Molecular docking study depicted that hydrophobic interaction (pi–pi stacking) plays a crucial role in maintaining the stability of the complex, which was also supported by intermolecular analysis from MD simulation study. Principal component analysis suggested that the terminal ends along with the turns/loops connecting adjacent helix and strands exhibit a comparatively higher movement of main chain atoms in most of the complexes. MM/PBSA binding free energy study revealed that non-polar solvation (van der Waals and electrostatic) energy subsidizes significantly to the total binding energy, and the polar solvation energy opposes the binding agonists to GLP-1R. Overall, we provide structural features information about GLP-1R complexes that would be conducive for the discovery of new GLP-1R agonists in the future for the treatment of various metabolic diseases.Communicated by Ramaswamy H. Sarma 相似文献
993.
Kotha Laxma Reddy Y. Harish Kumar Reddy S. Satyanarayana 《Nucleosides, nucleotides & nucleic acids》2013,32(10):953-968
Four Ru(II) polypyridyl complexes, [Ru(bpy)2(7-NO2-dppz)]2+, [Ru(bpy)2(7-CH3-dppz)]2+, [Ru(phen)2(7-NO2-dppz)]2+, and [Ru(phen)2(7-CH3-dppz)]2+ (bpy = 2,2′-bipyridine, phen = 1,10-phenanthroline), (7-Nitro-dppz = 7-Nitro dipyrido[3,2-a:2′-3′-c]phenazine, 7-CH3-dppz = 7-Methyl dipyrido[3,2-a:2′-3′-c]phenazine), have been synthesized and characterized by IR, UV, elemental analysis, 1H NMR, 13C-NMR, and mass spectroscopy. The DNA-binding properties of the four complexes were investigated by spectroscopic and viscosity measurements. The results suggest that all four complexes bind to DNA via an intercalative mode. Under irradiation at 365 nm, all four complexes were found to promote the photocleavage of plasmid pBR 322 DNA. Toxicological effects of the selected complexes were performed on industrially important yeasts (eukaryotic microorganisms). 相似文献
994.
Prabhat Kumar Thakur Anil Kumar Mathur Shashi Bala Gautam Chandrajit Balomajumder Rahul 《Bioremediation Journal》2013,17(1):61-70
ABSTRACT A laboratory-scale biofilter unit packed with a mixture of compost, sugarcane bagasse, and granulated activated carbon (GAC) in the ratio of 55:30:15 by weight was used for a biofiltration study of air stream containing benzene, toluene, ethylbenzene, and o-xylene (BTEX). The effect of superficial velocity on mass transfer coefficient for the packing was studied by maintaining gas flow rates of 3, 4, 5, 6, and 8 L min?1 for inlet concentrations of 0.1, 0.4, and 0.8 g m?3 for each of benzene, toluene, ethylbenzene, and o-xylene. The maximum elimination capacity was found to be 20.92, 22.72, 20.73, and 18.94 g m?3 h?1 for BTEX, respectively, for stated flow rates. Removal efficiency of BTEX decreased from 99% to 71% for increasing inlet concentration from 0.1 to 0.8 g m?3. Gas film mass transfer coefficient predicted by modified Onda's equation was within ±10% of the experimental values. 相似文献
995.
Annan Sudarsan Arun Kumar Gurusamy Umamaheswaran Ramamoorthy Padmapriya Jayaraman Balachandar Chandrasekaran Adithan 《Molecular biology reports》2013,40(2):1275-1281
Myocardial infarction (MI) is a complex multi-factorial, polygenic disorder which results from an interaction between a person’s genetic makeup and various environmental factors. Nitric oxide (NO), a potent vasodilator produced by endothelial cells, plays an important role in the regulation of blood pressure, regional blood flow and also inhibits platelet aggregation, vascular smooth muscle cell proliferation and leukocyte adhesion to vascular endothelium. Our aim was to analyze the association of NOS3 (endothelial nitric oxide synthase 3) 894G>T and ?786T>C gene polymorphisms and MI risk in the South Indian population. A total of 287 MI patients, 279 risk control patients and 321 healthy controls were recruited for the retrospective study. Genotyping was done using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). There was no significant association observed between NOS3 894G>T, ?786T>C polymorphisms and MI. A significant difference was observed in the distribution of GT genotype of the NOS3 894G>T polymorphism between the cases and the risk controls (p = 0.05) but the odds ratio (0.6) did not show risk for MI. The present study showed lack of association between NOS3 gene polymorphisms and MI in South Indian population. 相似文献
996.
Ajay Kumar Shiva Kant Sukh Mahendra Singh 《Apoptosis : an international journal on programmed cell death》2013,18(12):1574-1585
The present investigation was undertaken to study the effect of in vitro exposure of Colo205, colonadenocarcinoma cells, to monocarboxylate transporter inhibitor α-cyano-4-hydroxycinnamate (αCHC) on cell survival and evolution of resistance to chemotherapeutic drug cisplatin. αCHC-treated Colo205 cells showed inhibition of survival accompanied by an augmented induction of apoptosis. Changes in cell survival properties were associated with alterations in lactate efflux, pH homeostasis, expression of glucose transporters, glucose uptake, HIF-1α, generation of nitric oxide, expression pattern of some key cell survival regulatory molecules: Bcl2, Bax, active caspase-3 and p53. Pretreatment of Colo205 cells with αCHC also altered their susceptibility to the cytotoxicity of cisplatin accompanied by altered expression of multidrug resistance regulating MDR1 and MRP1 genes. This study for the first time deciphers some of the key molecular events underlying modulation of cell survival of cancer cells of colorectal origin by αCHC and its contribution to chemosensitization against cisplatin. Thus these findings will be of immense help in further research for optimizing the use of αCHC for improving the chemotherapeutic efficacy of anticancer drugs like cisplatin. 相似文献
997.
The aim of the study was to explore the association of the angiotensin-converting enzyme (ACE) gene I/D polymorphism and the methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism with development of diabetic nephropathy in type 2 diabetes mellitus. Three groups were recruited during 2007–2011: 232 normal controls, 185 type 2 diabetics without nephropathy, and 407 type 2 diabetics with nephropathy. The ACE I/D and MTHFR C677T polymorphisms were examined using PCR and PCR-RFLP methods. We found no significant association of the ACE I/D polymorphism with diabetic nephropathy in genotype, allele, dominant, and recessive models. We observed a significant association of MTHFR C677T with development of diabetic nephropathy in type 2 diabetics. The MTHFR C677T polymorphism plays a significant role in predisposition of renal insufficiency in diabetic patients. 相似文献
998.
Swapan Kumar Sarker Sanjay Saha Sonet Md. Mohasinul Haque Mahmuda Sharmin 《Ecological Research》2013,28(4):553-565
Tarap Hill Reserve, the largest upland reserve of Bangladesh, is situated along the Indo-Burma Biodiversity Hotspot. It encompasses the last remaining patches of natural vegetation in the Northeastern Tarap Mountain System and harbors 87 % of the nationally declared red-listed vascular plant species. Despite requiring high conservation priority, this is one of the least studied reserves in the tropics. In this study, we collected vegetation and soil (eight variables) data from 68 sample plots. We identified the tree communities by cluster analysis and verified them using the multi-response permutation procedure and detrended correspondence analysis. Species richness, diversity, and compositional similarity between the communities were also estimated. In total, 116 tree species representing 69 genera were recorded within the four identified tree community types. Finally, canonical correspondence analysis with associated Monte Carlo permutation tests (499 permutations) was performed to explore the patterns of variation in tree species distribution explained by the soil variables. Soil phosphorus, organic matter content, and pH were most closely correlated with tree compositional variation. Thus, conservation strategies that take into account variations in these influential soil factors may aid in the conservation of trees in the reserve. 相似文献
999.
Anukool Vaishnav Shekhar Jain Amrita Kasotia Sarita Kumari Rajarshi Kumar Gaur Devendra Kumar Choudhary 《Archives of microbiology》2013,195(8):571-577
To understand protective roles of nitric oxide against salt stress, the effects of exogenous sodium nitroprusside on activities of lipoxygenase, peroxidase, phenylalanine ammonialyase, catalase, superoxide dismutase enzymes, proline accumulation, and distribution of sodium in soybean plants under salt were determined. Application of sodium nitroprusside + bacterium enhanced plant growth-promotion characteristics, activities of different enzymes, and proline accumulation in the presence of sodium nitroprusside under salt stress. Treatment with NaCl at 200 mM and sodium nitroprusside (0.1 mM) reduced Na+ levels but increased K+ levels in leaves in comparison with the NaCl-treated plants. Correspondingly, the plants treated with exogenous sodium nitroprusside and NaCl maintained a lower ratio of [Na+]/[K+] in NaCl-stressed plants. 相似文献
1000.
On the basis of stereo specific information obtained from crystal structures of CDK2, indole and chromene analogues were designed by suitably substituting the pharmacophores on their moiety and docked with target protein for calculating binding affinities. The binding affinities are represented in glide score. (5E)-5-[(1-methyl-1H-indol-3-yl)methylidene]-2,4,6-trioxotetrahydro-2H-pyrimidin-1-ide (I1), (5E)-5-(1H-indol-3-ylmethylidene)-2,4,6-trioxotetrahydro-2H-pyrimidin-1-ide (I2) and 2-amino-4-(4-methyl phenyl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (C9) were selected for synthesis and biological testing based on vital interactions. (5E)-5-(1H-indol-3-ylmethylidene)-2,4,6-trioxotetrahydro-2H-pyrimidin-1-ide(I2) and 2-amino-4-(4-methyl phenyl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (C9) were proved to be active against MCF-7 and HeLa cell lines. 相似文献