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991.
Mariappan MR Narayan D Fadare O Sankarand JR 《The Yale journal of biology and medicine》2004,77(3-4):71-74
Much has been written about the philanthropist Elihu Yale and his life in the Americas and England, where he spent his beginnings and end. Less publicized is his life in India, where he spent the majority of his adult life and where he raised his family. A major contribution of Elihu Yale to medicine in India was his promotion of a local hospital in the major Indian trading port city of Madras. This essay briefly describes the history of that hospital and the medical college that grew out of it. 相似文献
992.
Bhuniya D Umrani D Dave B Salunke D Kukreja G Gundu J Naykodi M Shaikh NS Shitole P Kurhade S De S Majumdar S Reddy SB Tambe S Shejul Y Chugh A Palle VP Mookhtiar KA Cully D Vacca J Chakravarty PK Nargund RP Wright SD Graziano MP Singh SB Roy S Cai TQ 《Bioorganic & medicinal chemistry letters》2011,21(12):3596-3602
GPR91, a 7TM G-Protein-Coupled Receptor, has been recently deorphanized with succinic acid as its endogenous ligand. Current literature indicates that GPR91 plays role in various pathophysiology including renal hypertension, autoimmune disease and retinal angiogenesis. Starting from a small molecule high-throughput screening hit 1 (hGPR91 IC50: 0.8 μM)—originally synthesized in Merck for Bradykinin B1 Receptor (BK1R) program, systematic structure-activity relationship study led us to discover potent and selective hGPR91 antagonists e.g. 2c, 4c, and 5g (IC50: 7-35 nM; >1000 fold selective against hGPR99, a closest related GPCR; >100 fold selective in Drug Matrix screening). This initial work also led to identification of two structurally distinct and orally bio-available lead compounds: 5g (%F: 26) and 7e (IC50: 180 nM; >100 fold selective against hGPR99; %F: 87). A rat pharmacodynamic assay was developed to characterize the antagonists in vivo using succinate induced increase in blood pressure. Using two representative antagonists, 2c and 4c, the GPR91 target engagement was subsequently demonstrated using the designed pharmacodynamic assay. 相似文献
993.
Fungal degradation is emerging as a new powerful tool for the removal of potent neurotoxin pesticide, monocrotophos. Therefore, the present study is aimed at comparative characterization of monocrotophos degrading ability of three different fungal strains. Fungal strains were isolated from local agricultural soil by enrichment culture method, screened by gradient culture and identified as Aspergillus flavus, Fusarium pallidoroseum and Macrophomina sp. Growth kinetics revealed a direct positive influence of monocrotophos on the viability of fungal isolates. Fungal degradation was studied in phosphorus free liquid culture medium supplemented with 150 mg L?1 concentration of monocrotophos for a period of 15 days under optimized culture conditions. Degradation of MCP followed first order kinetics with k deg of 0.007, 0.002 and 0.005 day?1 and half life (t 1/2) of 4.21, 12.64 and 6.32 days for A. flavus, F. pallidoroseum and Macrophomina sp. respectively. To the best of our knowledge, it is the first report signifying the potential of monocrotophos degradation by Fusarium and Macrophomina sp. The results were further confirmed by HPTLC and FTIR which indicates disappearance of monocrotophos by hydrolytic cleavage of vinyl phosphate bond. Degradation of monocrotophos by fungal isolates was accompanied by the release of extracellular alkaline phosphatases, inorganic phosphates and ammonia. The overall comparative analysis followed the order of A. flavus > Macrophomina sp. > F. pallidoroseum. Therefore, it could be concluded from the study that these three different fungal strains could be effectively used as a potential candidate for the removal of monocrotophos from contaminated sites. 相似文献
994.
The plant growth regulator 2-ohloroethylphosphonic acid inhibited the elongation of growth inPhaseolus aureus seedlings. In comparison to the control, the polyphenol oxidase and peroxidase activity of treated seedlings was low up to
24 and 48 h of germination, respectively and that of phenylalanine ammonia-lyase and tyrosine ammonia-lyase was slightly less
at 120 h and that of α- and β-glucosidases were less at 48 and 72 h, respectively. At other stages of germination, it greatly
stimulated the activities of these enzymes.
Part of Ph. D. dissertation submitted by Y. K. Arora to Punjab Agricultural University, Ludhiana, India 相似文献
995.
996.
Koustav Maity Preeti Bajaj Namita Surolia Avadhesha Surolia Kaza Suguna 《Journal of biomolecular structure & dynamics》2013,31(5):973-983
Abstract The crystal structure of Rv0098, a long-chain fatty acyl-CoA thioesterase from Mycobacterium tuberculosis with bound dodecanoic acid at the active site provided insights into the mode of substrate binding but did not reveal the structural basis of substrate specificities of varying chain length. Molecular dynamics studies demonstrated that certain residues of the substrate binding tunnel are flexible and thus modulate the length of the tunnel. The flexibility of the loop at the base of the tunnel was also found to be important for determining the length of the tunnel for accommodating appropriate substrates. A combination of crystallographic and molecular dynamics studies thus explained the structural basis of accommodating long chain substrates by Rv0098 of M. tuberculosis. 相似文献
997.
Jeffry D. Sander Cherie L. Ramirez Samantha J. Linder Vikram Pattanayak Noam Shoresh Manching Ku Jennifer A. Foden Deepak Reyon Bradley E. Bernstein David R. Liu J. Keith Joung 《Nucleic acids research》2013,41(19):e181
Gene-editing nucleases enable targeted modification of DNA sequences in living cells, thereby facilitating efficient knockout and precise editing of endogenous loci. Engineered nucleases also have the potential to introduce mutations at off-target sites of action. Such unintended alterations can confound interpretation of experiments and can have implications for development of therapeutic applications. Recently, two improved methods for identifying the off-target effects of zinc finger nucleases (ZFNs) were described–one using an in vitro cleavage site selection method and the other exploiting the insertion of integration-defective lentiviruses into nuclease-induced double-stranded DNA breaks. However, application of these two methods to a ZFN pair targeted to the human CCR5 gene led to identification of largely non-overlapping off-target sites, raising the possibility that additional off-target sites might exist. Here, we show that in silico abstraction of ZFN cleavage profiles obtained from in vitro cleavage site selections can greatly enhance the ability to identify potential off-target sites in human cells. Our improved method should enable more comprehensive profiling of ZFN specificities. 相似文献
998.
999.
1000.
Vanessa R. M. Rodrigues Argha Mondal Jayashree A. Dharmadhikari Swapnesh Panigrahi Deepak Mathur Aditya K. Dharmadhikari 《PloS one》2013,8(4)
Optical traps (tweezers) are beginning to be used with increasing efficacy in diverse studies in the biological and biomedical sciences. We report here results of a systematic study aimed at enhancing the efficiency with which dielectric (transparent) materials can be optically trapped. Specifically, we investigate how truncation of the incident laser beam affects the strength of an optical trap in the presence of a circular aperture. Apertures of various sizes have been used by us to alter the beam radius, thereby changing the effective numerical aperture and intensity profile. We observe significant enhancement of the radial and axial trap stiffness when an aperture is used to truncate the beam compared to when no aperture was used, keeping incident laser power constant. Enhancement in trap stiffness persists even when the beam intensity profile is modulated. The possibility of applying truncation to multiple traps is explored; to this end a wire mesh is utilized to produce multiple trapping that also alters the effective numerical aperture. The use of a mesh leads to reduction in trap stiffness compared to the case when no wire mesh is used. Our findings lead to a simple-to-implement and inexpensive method of significantly enhancing optical trapping efficiency under a wide range of circumstances. 相似文献