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Systematic determination of genetic network architecture. 总被引:39,自引:0,他引:39
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G. S. Takimoto A. K. Cho J. A. Bevan 《Cellular and molecular life sciences : CMLS》1977,33(3):370-372
Summary The rate of accumulation and metabolism of3H-1-norepinephrine in the neuronal plexus of rat portal vein produces a small transmitter concentration gradient across the longitudinal smooth muscle layer which cannot account for the prejunctional supersensitivity observed and suggests localization of the alpha-adrenergic receptors adjacent to the nerve plexus.Acknowledgment. This work was supported by USPHS grant HE 8359 (JAB) and USPHS grant MH 23839 (AKC). 相似文献
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N-ethylmaleimide (NEM) 10 or 25 mg/kg b.wt, given s.c. 20 min beforehand, dose-dependently and significantly antagonizes the severity of gastric glandular ulcers produced by restraint at 4 degrees C (stress) for 2 h. These findings suggest that reduced activity of endogenous nonprotein sulfhydryl substances in gastric tissue does not worsen stress-induced ulceration in rat stomachs, unlike the deleterious effect its depletion is claimed to have on ethanol-evoked gastric mucosal damage. Thus, decreased SH activity appears not to play a role in the aetiology of mucosal ulcers due to stress. 相似文献
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Summary Stress produced severe mucosal ulcers, increased mucosal microcirculation and lowered mast cell counts in the glandular wall of rat stomachs. Mepyramine i.m. or metiamide i.p. effectively prevented both ulceration and microcirculatory changes but not stress-reduced mast cell counts.Acknowledgment. The authors thank Dr W.A.M. Duncan (Smith, Kline and French Labs Ltd, England) for the generous gift of metiamide. 相似文献
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Jeon YH Heo YS Kim CM Hyun YL Lee TG Ro S Cho JM 《Cellular and molecular life sciences : CMLS》2005,62(11):1198-1220
Phosphodiesterases (PDEs) are essential regulators of cyclic nucleotide signaling with diverse physiological functions. Because of their great market potential and therapeutic importance, PDE inhibitors became recognized as important therapeutic agents in the treatment of various diseases. Currently, there are seven PDE inhibitors on the market, and the pharmacological and safety evaluations of many drug candidates are in progress. Three-dimensional (3D) structures of catalytic domains of PDE 1, -3, -4, -5 and -9 in the presence of their inhibitors are now available, and can be utilized for rational drug design. Recent advances in molecular pharmacology of PDE isoenzymes resulted in identification of new potential applications of PDE inhibitors in various therapeutic areas, including dementia, depression and schizophrenia. This review will describe the latest advances in PDE research on 3D structural studies, the potential of therapeutic applications and the development of drug candidates.Received 30 November 2004; received after revision 24 January 2005; accepted 5 February 2005 相似文献
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Time-resolved optical spectroscopy is widely used to study vibrational and electronic dynamics by monitoring transient changes in excited state populations on a femtosecond timescale. Yet the fundamental cause of electronic and vibrational dynamics--the coupling between the different energy levels involved--is usually inferred only indirectly. Two-dimensional femtosecond infrared spectroscopy based on the heterodyne detection of three-pulse photon echoes has recently allowed the direct mapping of vibrational couplings, yielding transient structural information. Here we extend the approach to the visible range and directly measure electronic couplings in a molecular complex, the Fenna-Matthews-Olson photosynthetic light-harvesting protein. As in all photosynthetic systems, the conversion of light into chemical energy is driven by electronic couplings that ensure the efficient transport of energy from light-capturing antenna pigments to the reaction centre. We monitor this process as a function of time and frequency and show that excitation energy does not simply cascade stepwise down the energy ladder. We find instead distinct energy transport pathways that depend sensitively on the detailed spatial properties of the delocalized excited-state wavefunctions of the whole pigment-protein complex. 相似文献
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Global variation in copy number in the human genome 总被引:3,自引:0,他引:3
Redon R Ishikawa S Fitch KR Feuk L Perry GH Andrews TD Fiegler H Shapero MH Carson AR Chen W Cho EK Dallaire S Freeman JL González JR Gratacòs M Huang J Kalaitzopoulos D Komura D MacDonald JR Marshall CR Mei R Montgomery L Nishimura K Okamura K Shen F Somerville MJ Tchinda J Valsesia A Woodwark C Yang F Zhang J Zerjal T Zhang J Armengol L Conrad DF Estivill X Tyler-Smith C Carter NP Aburatani H Lee C Jones KW Scherer SW Hurles ME 《Nature》2006,444(7118):444-454
Copy number variation (CNV) of DNA sequences is functionally significant but has yet to be fully ascertained. We have constructed a first-generation CNV map of the human genome through the study of 270 individuals from four populations with ancestry in Europe, Africa or Asia (the HapMap collection). DNA from these individuals was screened for CNV using two complementary technologies: single-nucleotide polymorphism (SNP) genotyping arrays, and clone-based comparative genomic hybridization. A total of 1,447 copy number variable regions (CNVRs), which can encompass overlapping or adjacent gains or losses, covering 360 megabases (12% of the genome) were identified in these populations. These CNVRs contained hundreds of genes, disease loci, functional elements and segmental duplications. Notably, the CNVRs encompassed more nucleotide content per genome than SNPs, underscoring the importance of CNV in genetic diversity and evolution. The data obtained delineate linkage disequilibrium patterns for many CNVs, and reveal marked variation in copy number among populations. We also demonstrate the utility of this resource for genetic disease studies. 相似文献