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排序方式: 共有113条查询结果,搜索用时 31 毫秒
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Rajasekhar Ramakrishnan Janak D. Ramakrishnan 《Bulletin of mathematical biology》2010,72(8):2019-2046
Tracer studies are analyzed almost universally by multicompartmental models where the state variables are tracer amounts or
activities in the different pools. The model parameters are rate constants, defined naturally by expressing fluxes as fractions
of the source pools. We consider an alternative state space with tracer enrichments or specific activities as the state variables,
with the rate constants redefined by expressing fluxes as fractions of the destination pools. Although the redefinition may
seem unphysiological, the commonly computed fractional synthetic rate actually expresses synthetic flux as a fraction of the
product mass (destination pool). We show that, for a variety of structures, provided the structure is linear and stationary,
the model in the enrichment state space has fewer parameters than that in the activities state space, and is hence better
both to study identifiability and to estimate parameters. The superiority of enrichment modeling is shown for structures where
activity model unidentifiability is caused by multiple exit pathways; on the other hand, with a single exit pathway but with
multiple untraced entry pathways, activity modeling is shown to be superior. With the present-day emphasis on mass isotopes,
the tracer in human studies is often of a precursor, labeling most or all entry pathways. It is shown that for these tracer
studies, models in the activities state space are always unidentifiable when there are multiple exit pathways, even if the
enrichment in every pool is observed; on the other hand, the corresponding models in the enrichment state space have fewer
parameters and are more often identifiable. Our results suggest that studies with labeled precursors are modeled best with
enrichments. 相似文献
23.
Faster plasma vitamin E disappearance in smokers is normalized by vitamin C supplementation 总被引:1,自引:0,他引:1
Bruno RS Leonard SW Atkinson J Montine TJ Ramakrishnan R Bray TM Traber MG 《Free radical biology & medicine》2006,40(4):689-697
Vitamin E disappearance is accelerated in cigarette smokers due to their increased oxidative stress and is inversely correlated with plasma vitamin C concentrations. Therefore, we hypothesized that ascorbic acid supplementation (500 mg, twice daily; 2 weeks) would normalize smokers' plasma alpha- and gamma-tocopherol disappearance rates and conducted a double-blind, placebo-controlled, randomized crossover investigation in smokers (n=11) and nonsmokers (n=13) given a single dose of deuterium-labeled alpha- and gamma-tocopherols (50 mg each d6-RRR-alpha and d2-RRR-gamma-tocopheryl acetate). During the placebo trial, smokers, compared with nonsmokers, had significantly (P<0.05) greater alpha- and gamma-tocopherol fractional disappearance rates and shorter half-lives. Ascorbic acid supplementation doubled (P<0.0001) plasma ascorbic acid concentrations in both groups and attenuated smokers', but not nonsmokers', plasma alpha- and gamma-tocopherol (P<0.05) fractional disappearance rates by 25% and 45%, respectively. Likewise, smokers' plasma deuterium-labeled alpha- and gamma-tocopherol concentrations were significantly higher (P<0.05) at 72 h during ascorbic acid supplementation compared with placebo. Ascorbic acid supplementation did not significantly change (P>0.05) time of maximal or maximal-labeled alpha- and gamma-tocopherol concentrations. Smokers' plasma F2alpha-isoprostanes were approximately 26% higher than nonsmokers (P>0.05) and were not affected by ascorbic acid supplementation in either group (P>0.05). In summary, cigarette smoking increased plasma alpha- and gamma-tocopherol fractional disappearance rates, suggesting that the oxidative stress from smoking oxidizes tocopherols and that plasma ascorbic acid reduces alpha- and gamma-tocopheroxyl radicals to nonoxidized forms, thereby decreasing vitamin E disappearance in humans. 相似文献
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Comprehensive clone sets representing the entire genome now exist for a large number of organisms. The Gateway entry clone sets are a particularly useful means to study gene function, given the ease of introduction into any Gateway-suitable destination vector. We have adapted a bacterial two-hybrid system for use with Gateway entry clone sets, such that potential interactions between proteins encoded within these clone sets can be determined by new destination vectors. We show that utilizing the Gateway clone sets for Francisella tularensis and Vibrio cholerae, known interactions between F. tularensis IglA and IglB and V. cholerae VipA and VipB could be confirmed with these destination vectors. Moreover, the introduction of unique tags into each vector allowed for visualization of the expressed hybrid proteins via Western immunoblot. This Gateway-suitable bacterial two-hybrid system provides a new tool for rapid screening of protein-protein interactions. 相似文献
26.
Ahmed Kamal D. Rajasekhar Reddy M. Kashi Reddy G. Balakishan T. Basha Shaik Mukesh Chourasia G. Narahari Sastry 《Bioorganic & medicinal chemistry》2009,17(4):1557-1572
C2-Fluoro substituted DC-81, and its dimers that comprise of two C2-fluoro substituted DC-81 subunits tethered to their C8-position through simple alkane spacers as well as piperazine moiety side-armed with symmetrical alkyloxy spacers have been designed and synthesized. These fluoro substituted pyrrolo[2,1-c][1,4]benzodiazepines have shown remarkable DNA-binding ability and most of them possess promising anticancer activity, having GI50 values in micromolar to nanomolar concentration range. DNA thermal denaturation studies show that some of these compounds (14a–c and 15) increase the ΔTm values in the range of 28.9–38 °C, and this is further confirmed by the restriction endonuclease studies. This study illustrates the importance of introducing fluoro substitution at the C2-position apart from the incorporation of a piperazine ring in between the alkyloxy linker for enhancement of the DNA-binding ability in comparison to DSB-120 and SJG-136 (ΔTm = 10.2 and 25.7 °C). Moreover, the variations in the DNA-binding ability with respect to fluoro substitution in this class of dimers has been investigated by molecular modeling studies. Some representative C2-fluoro substituted dimers (8a and 14a) have also exhibited significant anticancer activity in the 60 cancer cell line assay of the National Cancer Institute (NCI). 相似文献
27.
Dell RB Holleran S Ramakrishnan R 《ILAR journal / National Research Council, Institute of Laboratory Animal Resources》2002,43(4):207-213
Scientists who use animals in research must justify the number of animals to be used, and committees that review proposals to use animals in research must review this justification to ensure the appropriateness of the number of animals to be used. This article discusses when the number of animals to be used can best be estimated from previous experience and when a simple power and sample size calculation should be performed. Even complicated experimental designs requiring sophisticated statistical models for analysis can usually be simplified to a single key or critical question so that simple formulae can be used to estimate the required sample size. Approaches to sample size estimation for various types of hypotheses are described, and equations are provided in the Appendix. Several web sites are cited for more information and for performing actual calculations 相似文献
28.
BACKGROUND: Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycaemia. Increased oxidative stress and decreased antioxidant levels are the leading cause of diabetes and diabetic complications. So it is felt that supplementation of antioxidants may be useful in controlling the glucose levels and to postpone the occurrence of diabetic complications. The objective of our study is to find the influence of antioxidant supplementation (L-ascorbic acid) on tolbutamide activity in normal and diabetic rats. METHODS: L- ascorbic acid/tolbutamide/L-ascorbic acid + tolbutamide were administered orally to 3 different groups of albino rats of either sex in normal and diabetic condition. Blood samples were collected from retro-orbital puncture at different time intervals and were analyzed for blood glucose by GOD-POD method. Diabetes was induced by alloxan 100 mg/kg body weight administered by I.P route. RESULTS: L-ascorbic acid/ tolbutamide produced hypoglycaemic activity in a dose dependant manner in normal and diabetic condition. In the presence of L-ascorbic acid, tolbuatmide produced early onset of action and maintained for longer period compared to tolbutamide matching control. CONCLUSION: Supplementation of antioxidants like L-ascorbic acid was found to improve tolbutamide response in normal and diabetic rats. 相似文献
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Tamsyn Derrick Chrissy h. Roberts Megha Rajasekhar Sarah E. Burr Hassan Joof Pateh Makalo Robin L. Bailey David C. W. Mabey Matthew J. Burton Martin J. Holland 《PLoS neglected tropical diseases》2013,7(3)