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51.
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Kubota N Inayoshi Y Satoh N Fukuda T Iwai K Tomoda H Kohara M Kataoka K Shimamoto A Furuichi Y Nomoto A Naganuma A Kuge S 《FEBS letters》2012,586(16):2318-2325
Hepatitis C virus core protein (Core) contributes to HCV pathogenicity. Here, we demonstrate that Core impairs growth in budding yeast. We identify HSP90 inhibitors as compounds that reduce intracellular Core protein level and restore yeast growth. Our results suggest that HSC90 (Hsc82) may function in the protection of the nascent Core polypeptide against degradation in yeast and the C-terminal region of Core corresponding to the organelle-interaction domain was responsible for Hsc82-dependent stability. The yeast system may be utilized to select compounds that can direct the C-terminal region to reduce the stability of Core protein. 相似文献
53.
Kenichiro Nagai Nobuhiro Koyama Noriko Sato Chisato Yanagisawa Hiroshi Tomoda 《Bioorganic & medicinal chemistry letters》2012,22(24):7739-7741
Synthesis of calpinactam 1, a fungal antimycobacterial metabolite, utilizing solid-phase peptide synthesis is described. To explore the structure–activity relationships of 1, its derivatives with different amino acids were also synthesized on the basis of the same synthetic strategy. These derivatives were examined for antimycobacterial activity against Mycobacterium smegmatis. Among them, only peptide 6d having d-Ala in place of d-Glu showed moderate activity. 相似文献
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Liang Y Arakawa K Ueta K Matsushita Y Kuriyama C Martin T Du F Liu Y Xu J Conway B Conway J Polidori D Ways K Demarest K 《PloS one》2012,7(2):e30555
Background
Canagliflozin is a sodium glucose co-transporter (SGLT) 2 inhibitor in clinical development for the treatment of type 2 diabetes mellitus (T2DM).Methods
14C-alpha-methylglucoside uptake in Chinese hamster ovary-K cells expressing human, rat, or mouse SGLT2 or SGLT1; 3H-2-deoxy-d-glucose uptake in L6 myoblasts; and 2-electrode voltage clamp recording of oocytes expressing human SGLT3 were analyzed. Graded glucose infusions were performed to determine rate of urinary glucose excretion (UGE) at different blood glucose (BG) concentrations and the renal threshold for glucose excretion (RTG) in vehicle or canagliflozin-treated Zucker diabetic fatty (ZDF) rats. This study aimed to characterize the pharmacodynamic effects of canagliflozin in vitro and in preclinical models of T2DM and obesity.Results
Treatment with canagliflozin 1 mg/kg lowered RTG from 415±12 mg/dl to 94±10 mg/dl in ZDF rats while maintaining a threshold relationship between BG and UGE with virtually no UGE observed when BG was below RTG. Canagliflozin dose-dependently decreased BG concentrations in db/db mice treated acutely. In ZDF rats treated for 4 weeks, canagliflozin decreased glycated hemoglobin (HbA1c) and improved measures of insulin secretion. In obese animal models, canagliflozin increased UGE and decreased BG, body weight gain, epididymal fat, liver weight, and the respiratory exchange ratio.Conclusions
Canagliflozin lowered RTG and increased UGE, improved glycemic control and beta-cell function in rodent models of T2DM, and reduced body weight gain in rodent models of obesity. 相似文献56.
Kenichi Nonaka Hidetoshi Miyazaki Masato Iwatsuki Kazuro Shiomi Hiroshi Tomoda Satoshi ōmura Rokuro Masuma 《Mycoscience》2012,53(4):312-318
Staphylotrichum boninense, a new hyphomycete classified in the Chaetomiaceae (Ascomycota), was isolated from soils in the Bonin Islands, Japan. It is characterized morphologically by the production of yellow-orange colonies and subglobose holoblastic conidia. Morphologically the species is similar to S. coccosporum, but it is significantly different from S. coccosporum in phylogeny and also differs with respect to its secondary metabolite profile. 相似文献
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Effects of thyroid hormones and their metabolites such as L-T1, L-T2, L-T3 and L-T4 on human erythrocyte acetylcholine esterase were studied. The activity of the enzyme of intact erythrocytes was not affected by these hormones, though studied under various conditions. The physiological significance of the binding of these hormones to erythrocyte membranes remains unclear. Our results indicate that the acetylcholine esterase is not a suitable enzyme for cytochemical bioassay for thyroid hormones. 相似文献
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Choline Kinase and Phosphorylcholine Phosphatase in Plants 总被引:13,自引:7,他引:6
Choline kinase was present in barley and wheat roots and leaves of barley, wheat, tobacco, spinach and squash plants. The kinase was purified 25-fold from spinach leaves. The enzyme had a broad pH optimum between 7.5 and 10.0. Mg(++) was required for activity and in the presence of Mg(++) the enzyme was relatively stable. Maximum enzyme activity was obtained when the Mg(++): ATP ratio was 1:1. The K(m) was 1 x 10(-4)m. The kinase from leaves was similar to that from rapeseed or from yeast, except that the leaf and seed enzymes were not inhibited by compounds which attach sulfhydryl groups.Only a very slow hydrolysis of phosphorylcholine by similar plant extracts was observed. This phosphatase activity was purified 200- or 300-fold and appeared to be caused by a nonspecific acid phosphatase.The activity of both the kinase and the phosphatase did not seem sufficient to account for the rapid equilibration of the large phosphorylcholine reservoir of plants with exogenous P(32)-labeled orthophosphate. 相似文献