全文获取类型
收费全文 | 118篇 |
免费 | 13篇 |
国内免费 | 1篇 |
出版年
2023年 | 1篇 |
2022年 | 3篇 |
2021年 | 5篇 |
2020年 | 3篇 |
2019年 | 3篇 |
2018年 | 8篇 |
2017年 | 3篇 |
2016年 | 7篇 |
2015年 | 11篇 |
2014年 | 12篇 |
2013年 | 9篇 |
2012年 | 10篇 |
2011年 | 13篇 |
2010年 | 3篇 |
2009年 | 4篇 |
2008年 | 6篇 |
2007年 | 5篇 |
2006年 | 6篇 |
2005年 | 4篇 |
2004年 | 2篇 |
2003年 | 2篇 |
2002年 | 3篇 |
2000年 | 1篇 |
1998年 | 1篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1985年 | 1篇 |
1976年 | 1篇 |
1974年 | 1篇 |
1961年 | 1篇 |
排序方式: 共有132条查询结果,搜索用时 15 毫秒
81.
The Gal10p (UDP-Galactose 4-epimerase) protein is known for regulation of D-galactose metabolism. It catalyzes the inter-conversion between UDPgalactose and UDP-glucose. Knowledge of protein structure, neighboring interacting partners as well as functional residues of the Gal10p is crucial for carry out its function. These problems are still uncovered in case of the Epimerase enzyme. Structure of Epimerase enzyme has already been determined in S.cerevisiae and E.coli, however, no structural information for this protein is available for K.lactis. We used the homology modeling approach to model the structure of Gal10p in K.lactis. Furthermore, functional residues were predicted for modeled Gal10 protein and the strength of interaction between Gal10p and other Gal proteins was carried out by protein -protein interaction studies. The interaction studies revealed that the affinity of Gal10p for other Gal proteins vary in different organisms. Sequence and structure comparison of Epimerase enzyme showed that the orthologs in K.lactis and S.cervisiae are more similar to each other as compared to the ortholog in E.coli .The studies carried by us will help in better understanding of the galactose metabolism. The above studies may be applied to Human Gal10p, where it can help in gaining useful insight into Galactosemia disease. 相似文献
82.
Kumar S Earla R Jin M Mitra AK Kumar A 《Biochemical and biophysical research communications》2010,402(1):163-167
Cytochrome P450 3A4 (CYP3A4) is the most abundant CYP enzyme in the liver and metabolizes approximately 50% of the drugs, including antiretrovirals. Although CYP3A4 induction by ethanol and impact of CYP3A4 on drug metabolism and toxicity is known, CYP3A4-ethanol physical interaction and its impact on drug binding, inhibition, or metabolism is not known. Therefore, we studied the effect of ethanol on binding and inhibition of CYP3A4 with a representative protease inhibitor, nelfinavir, followed by the effect of alcohol on nelfinavir metabolism. Our initial results showed that methanol, ethanol, isopropanol, isobutanol, and isoamyl alcohol bind in the active site of CYP3A4 and exhibit type I spectra. Among these alcohol compounds, ethanol showed the lowest KD (5.9 ± 0.34 mM), suggesting its strong binding affinity with CYP3A4. Ethanol (20 mM) decreased the KD of nelfinavir by >5-fold (0.041 ± 0.007 vs. 0.227 ± 0.038 μM). Similarly, 20 mM ethanol decreased the IC50 of nelfinavir by >3-fold (2.6 ± 0.5 vs. 8.3 ± 3.1 μM). These results suggest that ethanol facilitates binding of nelfinavir with CYP3A4. Furthermore, we performed nelfinavir metabolism using LCMS. Although ethanol did not alter kcat, it decreased the Km of nelfinavir, suggesting a decrease in catalytic efficiency (kcat/Km). This is an important finding because alcoholism is prevalent in HIV-1-infected persons and alcohol is shown to decrease the response to antiretroviral therapy. 相似文献
83.
Impact of pesticides on soil microbiological parameters and possible bioremediation strategies 总被引:1,自引:0,他引:1
Ashim Chowdhury Saswati Pradhan Monidipta Saha Nilanjan Sanyal 《Indian journal of microbiology》2008,48(1):114-127
Intensive agriculture is spectacularly successful since last couple of decades due to the inputs viz; fertilizers and pesticides
along with high yielding varieties. The mandate for agriculture development was to feed and adequate nutrition supply to the
expanding population by side the agriculture would be entering to into new area of commercial and export orientation. The
attention of public health and proper utilization natural resources are also the main issues related with agriculture development.
Concern for pesticide contamination in the environment in the current context of pesticide use has assumed great importance
[1]. The fate of the pesticides in the soil environment in respect of pest control efficacy, non-target organism exposure
and offsite mobility has been given due consideration [2]. Kinetics and pathways of degradation depend on abiotic and biotic
factors [6], which are specific to a particular pesticide and therefore find preference. Adverse effect of pesticidal chemicals
on soil microorganisms [3], may affect soil fertility [4] becomes a foreign chemicals major issue. Soil microorganisms show
an early warning about soil disturbances by foreign chemicals than any other parameters.
But the fate and behavior of these chemicals in soil ecosystem is very important since they are degraded by various factors
and have the potential to be in the soil, water etc. So it is indispensable to monitor the persistence, degradation of pesticides
in soil and is also necessary to study the effect of pesticide on the soil quality or soil health by in depth studies on soil
microbial activity.
The removal of metabolites or degraded products should be removed from soil and it has now a day’s primary concern to the
environmentalist. Toxicity or the contamination of pesticides can be reduced by the bioremediation process which involves
the uses of microbes or plants. Either they degrade or use the pesticides by various co metabolic processes. 相似文献
84.
Moberg KH Mukherjee A Veraksa A Artavanis-Tsakonas S Hariharan IK 《Current biology : CB》2004,14(11):965-974
BACKGROUND: The Myc oncoprotein is an important regulator of cellular growth in metazoan organisms. Its levels and activity are tightly controlled in vivo by a variety of mechanisms. In normal cells, Myc protein is rapidly degraded, but the mechanism of its degradation is not well understood. RESULTS: Here we present genetic and biochemical evidence that Archipelago (Ago), the F box component of an SCF-ubiquitin ligase and the Drosophila ortholog of a human tumor suppressor, negatively regulates the levels and activity of Drosophila Myc (dMyc) protein in vivo. Mutations in archipelago (ago) result in strongly elevated dMyc protein levels and increased tissue growth. Genetic interactions indicate that ago antagonizes dMyc function during development. Archipelago binds dMyc and regulates its stability, and the ability of Ago to bind dMyc in vitro correlates with its ability to inhibit dMyc accumulation in vivo. CONCLUSIONS: Our data indicate that archipelago is an important inhibitor of dMyc in developing tissues. Because archipelago can also regulate Cyclin E levels and Notch activity, these results indicate how a single F box protein can be responsible for the degradation of key components of multiple pathways that control growth and cell cycle progression. 相似文献
85.
86.
87.
Xiaoyan Yang Hoang M. Trinh Vibhuti Agrahari Ye Sheng Dhananjay Pal Ashim K. Mitra 《AAPS PharmSciTech》2016,17(2):294-306
This study was conducted to develop formulations of hydrocortisone butyrate (HB)-loaded poly(d,l-lactic-co-glycolic acid) nanoparticles (PLGA NP) suspended in thermosensitive gel to improve ocular bioavailability of HB for the treatment of bacterial corneal keratitis. PLGA NP with different surfactants such as polyvinyl alcohol (PVA), pluronic F-108, and chitosan were prepared using oil-in-water (O/W) emulsion evaporation technique. NP were characterized with respect to particle size, entrapment efficiency, polydispersity, drug loading, surface morphology, zeta potential, and crystallinity. In vitro release of HB from NP showed a biphasic release pattern with an initial burst phase followed by a sustained phase. Such burst effect was completely eliminated when nanoparticles were suspended in thermosensitive gels and zero-order release kinetics was observed. In HCEC cell line, chitosan-emulsified NP showed the highest cellular uptake efficiency over PVA- and pluronic-emulsified NP (59.09?±?6.21%, 55.74?±?6.26%, and 62.54?±?3.30%, respectively) after 4 h. However, chitosan-emulsified NP indicated significant cytotoxicity of 200 and 500 μg/mL after 48 h, while PVA- and pluronic-emulsified NP exhibited no significant cytotoxicity. PLGA NP dispersed in thermosensitive gels can be considered as a promising drug delivery system for the treatment of anterior eye diseases. 相似文献
88.
A series of stereoisomeric prodrugs have been designed to examine efficacy in generating higher corneal absorption relative to prednisolone. Prodrugs have been studied and identified with LC/MS/MS and NMR analyses. Prodrugs have been characterized for aqueous solubility, buffer stability, and cytotoxicity. Cellular uptake and permeability studies have been conducted across MDCK-MDR1 cells to determine prodrug affinity towards P-glycoprotein (P-gp) and peptide transporters. Enzyme-mediated degradation of prodrugs has been determined using Statens Seruminstitut rabbit cornea (SIRC) cell homogenates. Prodrugs exhibited higher aqueous solubility relative to prednisolone. Prodrugs circumvented P-gp-mediated cellular efflux and were recognized by peptide transporters. Prodrugs (DP, DDP) produced with d-isomers (d-valine) were significantly stable against both chemical and enzymatic hydrolyses. The order of degradation rate constants observed in chemical and enzymatic hydrolyses were in the same order, i.e., l-valine-l-valine-prednisolone (LLP)?>?l-valine-d-valine-prednisolone (LDP)?>?d-valine-l-valine-prednisolone (DLP)?>?d-valine-d-valine-prednisolone (DDP). Results obtained from this study clearly suggest that stereoisomeric prodrug approach is an effective strategy to overcome P-gp-mediated efflux and improve transcorneal permeability of prednisolone following topical administration. 相似文献
89.
90.
To study the metabolism of cholestanol in patients with cerebrotendinous xanthomatosis (CTX), we measured the cholestanol absorption, the cholesterol and cholestanol turnover, and the tissue content of sterols in two patients. Cholestanol absorption was approximately 5.0%. The rapid exchangeable pool of cholestanol was 233 mg, and the total exchangeable pool was 752 mg. The production rate of cholestanol in pool A was 39 mg/day. [4-14C]cholestanol was detected in the xanthomas, but neither [4-14C]cholestanol nor [4-14C]cholesterol was detected in peripheral nerves biopsied at 49 and 97 days after [4-14C]cholesterol given intravenously. Of the 18 tissues analyzed at biopsy and autopsy, the cholestanol content varied from 0.09 mg/g in psoas muscle to 76 mg/g in a cerebellar xanthoma. With the assumption that the cholestanol-to-cholesterol ratio is 1.0, the relative cholestanol-to-cholesterol ratio varied from 1.0 in plasma and liver to 30.0 in the cerebellar xanthoma; cholestanol was especially high in nerve tissue. Our data indicate that CTX patients absorb cholestanol from the diet. They have a higher than normal cholestanol production rate. Cholestanol was derived from cholesterol. In CTX patients, the blood-brain barrier was intact to the passage of [4-14C]cholesterol and [4-14C]cholestanol. The deposition of large amounts of cholestanol (up to 30% of total sterols in cerebellum) in nerve tissues must have an important role in the neurological symptoms in CTX patients. In view of the intact blood-brain barrier, several other explanations for the large amounts of cholestanol in the brain were postulated. 相似文献