全文获取类型
收费全文 | 718篇 |
免费 | 49篇 |
国内免费 | 1篇 |
专业分类
768篇 |
出版年
2023年 | 5篇 |
2022年 | 10篇 |
2021年 | 18篇 |
2020年 | 9篇 |
2019年 | 13篇 |
2018年 | 15篇 |
2017年 | 13篇 |
2016年 | 23篇 |
2015年 | 34篇 |
2014年 | 40篇 |
2013年 | 52篇 |
2012年 | 46篇 |
2011年 | 58篇 |
2010年 | 29篇 |
2009年 | 24篇 |
2008年 | 40篇 |
2007年 | 50篇 |
2006年 | 43篇 |
2005年 | 18篇 |
2004年 | 35篇 |
2003年 | 29篇 |
2002年 | 24篇 |
2001年 | 7篇 |
2000年 | 14篇 |
1999年 | 10篇 |
1998年 | 14篇 |
1997年 | 3篇 |
1996年 | 1篇 |
1995年 | 3篇 |
1994年 | 6篇 |
1993年 | 3篇 |
1992年 | 9篇 |
1991年 | 8篇 |
1990年 | 5篇 |
1989年 | 7篇 |
1988年 | 1篇 |
1987年 | 9篇 |
1986年 | 9篇 |
1985年 | 6篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1981年 | 6篇 |
1980年 | 2篇 |
1977年 | 3篇 |
1976年 | 3篇 |
1975年 | 3篇 |
1970年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有768条查询结果,搜索用时 15 毫秒
91.
92.
Conventional dendrimers are spherical symmetrically branched polymers ending with active surface functional groups. Polyamidoamine (PAMAM) dendrimers have been widely studied as gene delivery vectors and have proven effective at delivering DNA to cells in vitro. However, higher‐generation (G4‐G8) PAMAM dendrimers exhibit toxicity due to their high cationic charge density and this has limited their application in vitro and in vivo. Another limitation arises when attempts are made to functionalize spherical dendrimers as targeting moieties cannot be site‐specifically attached. Therefore, we propose that lower‐generation asymmetric dendrimers, which are likely devoid of toxicity and to which site‐specific attachment of targeting ligands can be achieved, would be a viable alternative to currently available dendrimers. We synthesized and characterized a series of peptide‐based asymmetric dendrimers and compared their toxicity profile and ability to condense DNA to spherical PAMAM G1 dendrimers. We show that asymmetric dendrimers are minimally toxic and condense DNA into stable toroids which have been reported necessary for efficient cell transfection. This paves the way for these systems to be conjugated with targeting ligands for gene delivery in vitro and in vivo. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
93.
The study has been designed to investigate the anti-diabetic effects of cesium aqua (N,N′-ethylene (salicylideneiminato)-5-sulfonato) oxovanadium (IV) dihydrate (VO(salen-SO3)), an organic vanadium compound, in streptozotocin-induced diabetic rats. VO(salen-SO3) was orally administrated to diabetic rats at the dose of 0.3 mg/ml through drinking water for 24 days. Blood glucose level
was significantly declined, and oral glucose tolerance was improved after VO(salen-SO3) treatment. Moreover, liver and muscle glycogen concentrations were markedly increased in VO(salen-SO3)-treated diabetic rats. On the other hand, aspartate amino transferase and blood urea nitrogen in serum were significantly
decreased after treatment with VO(salen-SO3). Take together, these results suggested that VO(salen-SO3) may be of potential value in the therapy of diabetic symptom and hyperglycemia-induced hepatic and renal dysfunction. 相似文献
94.
Chee GL Bhattarai B Daniel Gietz R Alrushaid S Nitiss JL Hasinoff BB 《Bioorganic & medicinal chemistry》2012,20(4):1494-1501
Bethoxazin is a new broad spectrum industrial microbicide with applications in material and coating preservation. However, little is known of its reactivity profile and mechanism of action. In this study, we examined the reactivity of bethoxazin toward biologically important nucleophilic groups using UV-vis spectroscopy and LC-MS/MS techniques and found the molecule to be highly electrophilic. Bethoxazin reacted with molecules containing free sulfhydryl groups such as GSH and human serum albumin to form covalent adducts that were detectable by MS, but did not react with amino, carboxylic, phenolic, amino oxo, alcoholic, and phosphate functional groups. Bethoxazin potently inhibited the catalytic activity of yeast DNA topoisomerase II and the growth of yeast BY4742 cells at low micromolar concentrations. However, the reduced form of bethoxazin and GSH-treated bethoxazin were both inactive in these assays. The experimentally determined relative reactivity of bethoxazin and its reduced form analog correlated with their biological activities as well as their quantum-mechanically calculated electrophilicity properties. Taken together, the results suggest that bethoxazin may exert its microbicidal action by reacting with sensitive endogenous sulfhydryl biomolecules of microbial cells. Consistent with this view, the inhibitory activity of bethoxazin on topoisomerase II may be due to its ability to react with critical free cysteine sulfhydryl groups on the enzyme. Our studies have provided for the first time a better understanding of the reactivity of bethoxazin, as well as some insights into the mechanism by which the compound exerts its microbicidal action. 相似文献
95.
Lagu B Lebedev R Pio B Yang M Pelton PD 《Bioorganic & medicinal chemistry letters》2007,17(12):3491-3496
A number of RXR modulators with novel structural features were synthesized and screened in the functional assays. The synthesis and the structure-activity relationship within the series of compounds will be presented. Some in vivo data generated in the models for dyslipidemia and diabetes will also be presented. 相似文献
96.
97.
98.
99.
We report a simple square capillary-based cell affinity chromatography device that utilizes a coating of aptamers for selective capture of target cancer cells from a flowing suspension. The device consists of a square capillary with an inner diameter of roughly five cell diameters, connected via Teflon tubing to a syringe. Aptamers are immobilized on the inner surface of the capillary through biotin-avidin chemistry, the extent of which can be controlled by adjusting the aptamer concentration. Introduction of different cell types into separate devices, as well as mixtures of target and non-target cells, demonstrated that aptamer-target cells can be captured in significantly higher concentrations compared to non-target cells. Once optimized, 91.1 ± 3.5% capture efficiency of target leukemia cells was reported, as well as 97.2 ± 2.8% and 83.6 ± 5.8% for two different colon cancer cell lines. In addition, cells captured in the device were imaged, and the square capillary exhibited better optical properties than standard cylindrical capillaries, leading to the detection of leukemia cells in blood samples. Compared to current microfluidic cell affinity devices, this capture device requires no complicated design or fabrication steps. By providing a simple means of detecting and imaging cancer cells in the blood, this work has potential to directly assist clinicians in determining disease prognosis and measuring therapeutic response. 相似文献
100.
The microbial and enzymatic degradation of a new energetic compound, 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20), is not well understood. Fundamental knowledge about the mechanism of microbial degradation of CL-20 is essential to allow the prediction of its fate in the environment. In the present study, a CL-20-degrading denitrifying strain capable of utilizing CL-20 as the sole nitrogen source, Pseudomonas sp. strain FA1, was isolated from a garden soil. Studies with intact cells showed that aerobic conditions were required for bacterial growth and that anaerobic conditions enhanced CL-20 biotransformation. An enzyme(s) involved in the initial biotransformation of CL-20 was shown to be membrane associated and NADH dependent, and its expression was up-regulated about 2.2-fold in CL-20-induced cells. The rates of CL-20 biotransformation by the resting cells and the membrane-enzyme preparation were 3.2 +/- 0.1 nmol h(-1) mg of cell biomass(-1) and 11.5 +/- 0.4 nmol h(-1) mg of protein(-1), respectively, under anaerobic conditions. In the membrane-enzyme-catalyzed reactions, 2.3 nitrite ions (NO(2)(-)), 1.5 molecules of nitrous oxide (N(2)O), and 1.7 molecules of formic acid (HCOOH) were produced per reacted CL-20 molecule. The membrane-enzyme preparation reduced nitrite to nitrous oxide under anaerobic conditions. A comparative study of native enzymes, deflavoenzymes, and a reconstituted enzyme(s) and their subsequent inhibition by diphenyliodonium revealed that biotransformation of CL-20 is catalyzed by a membrane-associated flavoenzyme. The latter catalyzed an oxygen-sensitive one-electron transfer reaction that caused initial N denitration of CL-20. 相似文献