全文获取类型
收费全文 | 252篇 |
免费 | 14篇 |
出版年
2023年 | 1篇 |
2022年 | 1篇 |
2021年 | 4篇 |
2020年 | 6篇 |
2019年 | 9篇 |
2018年 | 2篇 |
2017年 | 10篇 |
2016年 | 5篇 |
2015年 | 12篇 |
2014年 | 19篇 |
2013年 | 6篇 |
2012年 | 23篇 |
2011年 | 16篇 |
2010年 | 7篇 |
2009年 | 9篇 |
2008年 | 16篇 |
2007年 | 17篇 |
2006年 | 16篇 |
2005年 | 19篇 |
2004年 | 14篇 |
2003年 | 16篇 |
2002年 | 8篇 |
2001年 | 4篇 |
2000年 | 6篇 |
1999年 | 3篇 |
1998年 | 4篇 |
1996年 | 4篇 |
1995年 | 2篇 |
1993年 | 2篇 |
1991年 | 2篇 |
1980年 | 2篇 |
1963年 | 1篇 |
排序方式: 共有266条查询结果,搜索用时 15 毫秒
51.
Aslamuzzaman Kazi Sevil Ozcan Awet Tecleab Ying Sun Harshani R. Lawrence Sa?d M. Sebti 《The Journal of biological chemistry》2014,289(17):11906-11915
The proteasome inhibitor bortezomib is effective in hematologic malignancies such as multiple myeloma but has little activity against solid tumors, acts covalently, and is associated with undesired side effects. Therefore, noncovalent inhibitors that are less toxic and more effective against solid tumors are desirable. Structure activity relationship studies led to the discovery of PI-1840, a potent and selective inhibitor for chymotrypsin-like (CT-L) (IC50 value = 27 ± 0.14 nm) over trypsin-like and peptidylglutamyl peptide hydrolyzing (IC50 values >100 μm) activities of the proteasome. Furthermore, PI-1840 is over 100-fold more selective for the constitutive proteasome over the immunoproteasome. Mass spectrometry and dialysis studies demonstrate that PI-1840 is a noncovalent and rapidly reversible CT-L inhibitor. In intact cancer cells, PI-1840 inhibits CT-L activity, induces the accumulation of proteasome substrates p27, Bax, and IκB-α, inhibits survival pathways and viability, and induces apoptosis. Furthermore, PI-1840 sensitizes human cancer cells to the mdm2/p53 disruptor, nutlin, and to the pan-Bcl-2 antagonist BH3-M6. Finally, in vivo, PI-1840 but not bortezomib suppresses the growth in nude mice of human breast tumor xenografts. These results warrant further evaluation of a noncovalent and rapidly reversible proteasome inhibitor as potential anticancer agents against solid tumors. 相似文献
52.
Selmin Toplan Nuran Dariyerli Semra Ozdemir Dervis Ozcelik Emel U. Zengin Mehmet C. Akyolcu 《Biological trace element research》2013,152(3):373-378
The present study was conducted to explore the possible effects of different doses of lithium carbonate on thyroid functions, erythrocyte oxidant–antioxidant status, and osmotic fragility. Twenty-four Wistar-type male rats were equally divided into three groups: groups I and II received 0.1 and0.2 % lithium carbonate in their drinking water, respectively, for 30 days. The rats in group III served as controls, drinking tap water without added lithium. At the end of the experimental period, the erythrocyte osmotic fragility and the levels of triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) were measured in blood samples. Compared to controls, there was a statistically significant increase of TSH but decreases of the T3 and T4 levels in group II. Both experimental groups showed a statistically significant increase of the maximum osmotic fragility limit. The minimum osmotic fragility values of the animals in group II were statistically higher than those of controls. The standard hemolytic increment curve of both experimental groups was shifted to the right when compared to the curve obtained from the controls. Also, relative to controls, the activities of MDA and SOD were significantly higher and the GSH level lower in group II, but not so in group I. The results of the present study show that treatment with lithium carbonate may result in thyroid function abnormalities, increased oxidative damage, and possible compromise of the erythrocyte membrane integrity resulting from increased osmotic fragility. 相似文献
53.
Molecular imprinted polymers (MIP) as a recognition element for sensors are increasingly of interest and MIP-quartz crystal microbalance (QCM) have started to appear in the literature. In this study, we have combined quartz crystal microbalance with MIP to prepare a sensor using the ability of glucose to chelate of copper (II) ion of methacrylamidohistidine (MAH) monomer to create ligand exchange (LE) assembled monolayer which is suitable for glucose determination. The study includes the measurement of binding interaction of molecularly imprinted QCM sensor via ligand interaction, investigation of the pH effect on frequency shift and recognition selectivity studies of glucose-imprinted polymer with respect to methyl-alpha-d-glucopyranoside and sucrose. Bmax (number of binding sites) and K(D) (dissociation constant of the metal-chelate copolymer) were also calculated using Scathard plot and the detection limit was found as 0.07 mM. MIP showed higher glucose-binding affinity than a well-known glucose binding protein, conconavalin A. 相似文献
54.
Early detection of bladder cancer is particularly important since it dramatically affects the survival rates. However, neither urinary cytology nor tumor markers that are currently used are sensitive enough for the early detection of bladder cancer or recurrent disease. The ras genes are frequently mutated in cancer. In this study, we investigated the diagnostic potential of ras mutation analysis in urinary sediments of patients with bladder cancer using a single-strand conformation polymorphism analysis and polymerase chain reaction. Mutation in codon 12 of the H-ras gene was observed in 39% of the patients. Our results indicate that this approach may significantly improve diagnostic sensitivity in detecting bladder tumors. 相似文献
55.
N. OZCAN, C. CUNNINGHAM AND W.J. HARRIS. 1996. A gene encoding an enzyme which degrades cellulose ( end-1 ) was isolated from a library of Fibrobacter succinogenes SD35 DNA fragments and expressed in pUC18. The product of end-1 showed significant activity against carboxymethylcellulose but relatively minor activity against lichenan, xylan and avicel. The nucleotide sequence indicated a product of 388 amino acids with a molecular mass of 50.2 kDa. This was in agreement with the molecular size estimated by gel electrophoresis. No significant DNA sequence similarity was identified with any published endoglucanase. 相似文献
56.
57.
Alper Otunctemur Emin Ozbek Suleyman Sahin Levent Ozcan Murat Dursun Emre Can Polat Mustafa Cekmen Ozgur Doga Ozsoy Mustafa Erkoc Eyup Danis Muammer Bozkurt 《Andrologie》2016,26(1):1
Objective
Endothelial dysfunction and microvascular damage play a crurical role in the pathogenesis of erectile dysfunction (ED). Insulin-like growth factor-1 (IGF-1) is one of the growth factors that have a wide range of biologic effects. IGF-1 is an important mediator of cell growth, differentiation and transformation in various tissues. The purpose of the current study was to determine the association between IGF-1 levels and ED.Materials and methods
All men were evaluated for ED and divided into two groups: 80 patients suffering from ED for >?1 year and 80 subjects without ED were enrolled as a control group in this study. Diagnosis of ED was based on the International Index of Erectile Function Score-5. IGF-1 levels were measured in serum by an automated chemiluminescence immunoassay. The relationship between IGF-1 levels and ED scores in patients was statistically evaluated.Results
The mean age of patients in ED group was 60.4?±?11.3 years and 55.4?±?9.6 in control group. The plasma IGF-1 levels were significantly lower in ED than in control group (96.5?±?38.3 and 132.5?±?53.3 ng/ mL, respectively, P?<?0.001). The IGF-1 levels were positively correlated with ED score (r?=?0.623, P?<?0.01).Conclusion
In this study serum IGF-1 levels were found to be associated with endothelial dysfunction that predicts ED. Serum IGF-1 level appears to be a specific predictor of ED, and it might be used in early prediction of ED in male population.58.
Nuran Nabi Shiro Kominami Shigeki Takemori Tsuneo Omura 《Biochemical and biophysical research communications》1980,97(2):687-693
synthesis of mitochondrial cytochromes P-450(scc) and P-450(11-β), and microsomal cytochrome P-450(C-21) programmed by bovine adrenal cortex polysomes was carried out using rat liver cell sap and wheat germ lysate systems. Synthesis of P-450 proteins in the cell-free systems was determined by immunoprecipitation and immunoadsorption using mono-specific antibodies to each species of P-450, and the sizes of the products were analyzed by SDS-polyacrylamide gel electrophoresis. Both free and bound polysomes synthesized these three species of P-450 in the cell-free systems. P-450(scc) and P-450(C-21) were synthesized apparently as the mature size products, whereas P-450(11-β) was synthesized as a putative precursor approximately 5,000 daltons larger than the mature form. Mitochondrial and microsomal P-450 proteins seem to share common sites of synthesis in the cytoplasm of adrenal cortex cells. 相似文献
59.
Sevilay Inal Kabala Hulya Yagar Hakkı Mevlut Ozcan 《Preparative biochemistry & biotechnology》2019,49(5):511-520
AbstractOsteoporosis is a disease that is characterized by deterioration of bone tissue and increased risk of fracture as it leads to a decrease in bone mineral density, which is an important public health problem. Today, bone mineral density is measured by radiological techniques. Alternative techniques are needed because of the disadvantages such as excessive radiation intake, the cost of radiological techniques, and the necessity for specialist personnel for the devices. The quantitative determination of biochemical markers that play a role in bone mineralization may be a good alternative for the osteoporosis diagnosis and especially in the follow-up of treatment.In this study, a specific and sensitive immunological biosensor, which quantitatively determines the osteocalcin molecule, has been developed to be used in the early osteoporosis diagnosis and to evaluate the response to the drug treatment. Anti-osteocalcin antibody was immobilized onto gold electrode surface via covalent immobilization method by using 6-mercaptohexanol, 1,4-butanedioldiglycidyl ether, ethanolamine, and glutaraldehyde. Immobilization steps and biosensor characterization were specified by cyclic voltammetry and electrochemical impedance spectroscopy. The detection time and range of Ocn biosensor were determined as 45?min and 10–60?pg µL?1 Ocn concentration, respectively. The Ocn biosensor was successfully applied in artificial serum samples spiked with Ocn. 相似文献
60.
Phanerochaete chrysosporium soluble proteome as a prelude for the analysis of heavy metal stress response 总被引:1,自引:0,他引:1
A 2-D reference map in pI range 3-10 was constructed for the soluble protein fraction of Phanerochaete chrysosporium growing vegetatively under standard conditions. Functional annotation could be made for 517 spots out of 720 that were subjected to MALDI-TOF-MS analysis, according to the specific accession numbers from the P. chrysosporium genomic database. Further analysis of the data revealed 314 distinct ORFs, 118 of which yielded multiple spots on the master gel. Functional classification of the proteins was made according to the eukaryote orthologous groups defined in the organism's genome website. The functional class of PTMs, protein turnover and chaperones was represented with the highest number (63) of the identified ORFs. Six proteins were assigned to the hypothetical proteins and 29 were predicted to have a signal peptide sequence. Subcellular localization predictions were also made for the identified proteins. Of the protein spots detected on the master gel, 380 were found to be probably phosphorylated and 96 of these matched to the identified proteins. The reference map was efficiently used in the identification of the proteins differentially expressed under cadmium and copper stress. Three new ribosomal proteins as well as zinc-containing alcohol dehydrogenase, glucose-6-phosphate isomerase, flavonol/cinnamoyl-CoA reductase, H+-transporting two-sector ATPase, ribosomal protein S7, ribosomal protein S21e, elongation factor EF-1 alpha subunit were demonstrated as the most strongly induced. 相似文献