全文获取类型
收费全文 | 511篇 |
免费 | 19篇 |
出版年
2023年 | 3篇 |
2022年 | 16篇 |
2021年 | 18篇 |
2020年 | 10篇 |
2019年 | 16篇 |
2018年 | 10篇 |
2017年 | 17篇 |
2016年 | 20篇 |
2015年 | 18篇 |
2014年 | 25篇 |
2013年 | 32篇 |
2012年 | 39篇 |
2011年 | 34篇 |
2010年 | 30篇 |
2009年 | 10篇 |
2008年 | 36篇 |
2007年 | 39篇 |
2006年 | 31篇 |
2005年 | 34篇 |
2004年 | 24篇 |
2003年 | 27篇 |
2002年 | 13篇 |
2001年 | 11篇 |
2000年 | 8篇 |
1999年 | 2篇 |
1998年 | 2篇 |
1996年 | 1篇 |
1994年 | 1篇 |
1993年 | 2篇 |
1992年 | 1篇 |
排序方式: 共有530条查询结果,搜索用时 249 毫秒
1.
Tiffany M. Tsang Jeffrey S. Wiese Suleyman Felek Malte Kronshage Eric S. Krukonis 《PloS one》2013,8(12)
The Yersinia pestis adhesin Ail mediates host cell binding and facilitates delivery of cytotoxic Yop proteins. Ail from Y. pestis and Y. pseudotuberculosis is identical except for one or two amino acids at positions 43 and 126 depending on the Y. pseudotuberculosis strain. Ail from Y. pseudotuberculosis strain YPIII has been reported to lack host cell binding ability, thus we sought to determine which amino acid difference(s) are responsible for the difference in cell adhesion. Y. pseudotuberculosis YPIII Ail expressed in Escherichia coli bound host cells, albeit at ∼50% the capacity of Y. pestis Ail. Y. pestis Ail single mutants, Ail-E43D and Ail-F126V, both have decreased adhesion and invasion in E. coli when compared to wild-type Y. pestis Ail. Y. pseudotuberculosis YPIII Ail also had decreased binding to the Ail substrate fibronectin, relative to Y. pestis Ail in E. coli. When expressed in Y. pestis, there was a 30–50% decrease in adhesion and invasion depending on the substitution. Ail-mediated Yop delivery by both Y. pestis Ail and Y. pseudotuberculosis Ail were similar when expressed in Y. pestis, with only Ail-F126V giving a statistically significant reduction in Yop delivery of 25%. In contrast to results in E. coli and Y. pestis, expression of Ail in Y. pseudotuberculosis led to no measurable adhesion or invasion, suggesting the longer LPS of Y. pseudotuberculosis interferes with Ail cell-binding activity. Thus, host context affects the binding activities of Ail and both Y. pestis and Y. pseudotuberculosis Ail can mediate cell binding, cell invasion and facilitate Yop delivery. 相似文献
2.
Antoaneta Trendafilova Victoria Ivanova Miroslav Rangelov Milka Todorova Gulmira Ozek Suleyman Yur Temel Ozek Ina Aneva Ralitza Veleva Veselina Moskova‐Doumanova Jordan Doumanov Tanya Topouzova‐Hristova 《化学与生物多样性》2020,17(4)
Chlorogenic (5‐CQA), 1,5‐, 3,5‐, 4,5‐ and 3,4‐dicaffeoylquinic (DCQA) acids were identified and quantified in the methanol extracts of Inula oculus‐christi L., I. bifrons L., I. aschersoniana Janka var. aschersoniana, I. ensifolia L., I. conyza (Griess .) DC. and I. germanica L. by HPLC analysis. The amount of 5‐CQA varied from 5.48 to 28.44 mg/g DE and the highest content was detected in I. ensifolia. 1,5‐DCQA (4.05–55.25 mg/g DE) was the most abundant dicaffeoyl ester of quinic acid followed by 3,5‐DCQA, 4,5‐DCQA and 3,4‐DCQA. The extract of I. ensifolia showed the highest total phenolic content (119.92±0.95 mg GAE/g DE) and exhibited the strongest DPPH radical scavenging activity (69.41±0.55 %). I. bifrons extract was found to be the most active sample against ABTS.+ (TEAC 0.257±0.012 mg/mL) and the best tyrosinase inhibitor. The studied extracts demonstrated a low inhibitory effect towards acetylcholinesterase and possessed low cytotoxicity in concentration range from 10 to 300 μg/mL toward non‐cancer (MDCK II) and cancer (A 549) cells. 相似文献
3.
Syed Muhammad Hamid Mevlut Citir Erdem Murat Terzi Ismail Cimen Zehra Yildirim Asli Ekin Dogan Begum Kocaturk Umut Inci Onat Moshe Arditi Christian Weber Alexis TraynorKaplan Carsten Schultz Ebru Erbay 《EMBO reports》2020,21(12)
The ER‐bound kinase/endoribonuclease (RNase), inositol‐requiring enzyme‐1 (IRE1), regulates the phylogenetically most conserved arm of the unfolded protein response (UPR). However, the complex biology and pathology regulated by mammalian IRE1 cannot be fully explained by IRE1’s one known, specific RNA target, X box‐binding protein‐1 (XBP1) or the RNA substrates of IRE1‐dependent RNA degradation (RIDD) activity. Investigating other specific substrates of IRE1 kinase and RNase activities may illuminate how it performs these diverse functions in mammalian cells. We report that macrophage IRE1 plays an unprecedented role in regulating phosphatidylinositide‐derived signaling lipid metabolites and has profound impact on the downstream signaling mediated by the mammalian target of rapamycin (mTOR). This cross‐talk between UPR and mTOR pathways occurs through the unconventional maturation of microRNA (miR) 2137 by IRE1’s RNase activity. Furthermore, phosphatidylinositol (3,4,5) phosphate (PI(3,4,5)P3) 5‐phosphatase‐2 (INPPL1) is a direct target of miR‐2137, which controls PI(3,4,5)P3 levels in macrophages. The modulation of cellular PI(3,4,5)P3/PIP2 ratio and anabolic mTOR signaling by the IRE1‐induced miR‐2137 demonstrates how the ER can provide a critical input into cell growth decisions. 相似文献
4.
AbstractImmobilization of enzymes from different sources on various supports in designed systems increases enzymes’ stability by protecting the active site of it from undesired effect of reaction environment. Also, immobilization decreases the cost of separation and facilities the reuse of the enzymes. Therefore, the design of new immobilization enzyme preparations has been an inevitable area of modern biotechnology. Herein, Rhizomucor miehei lipase (RML) was immobilized on montmorillonite K-10 (MMT-RML) by adsorption and in polyvinyl alcohol (PVA-RML) by entrapment to obtain a more stable and active lipase preparation. The free and immobilized lipase preparations were characterized for p-nitrophenyl palmitate hydrolysis. The apparent Michaelis–Menten (Kmapp) constant was almost the same for the free RML and PVA-RML, whereas the corresponding value was 17.7-fold lower for MMT-RML. PVA-RML and MMT-RML have shown a 1.1 and 23.8 folds higher catalytic efficiency, respectively, than that of the free RML. The half-lives of PVA-RML and MMT-RML were found to be 7.4 and 3.4 times longer than the free RML at 35?°C, respectively. PVA-RML and MMT-RML maintained 65% and 87% of their initial activities after four reuses. These results showed that the catalytic performance of RML has improved significantly by immobilization. 相似文献
5.
Brestic Marian Yang Xinghong Li Xiangnan Allakhverdiev Suleyman I. 《Photosynthesis research》2021,150(1-3):1-3
Photosynthesis Research - 相似文献
6.
Adem Yildirim Sina Mozaffari-Jovin Ann-Kathrin Wallisch Jessica Schfer Sebastian E J Ludwig Henning Urlaub Reinhard Lührmann Uwe Wolfrum 《Nucleic acids research》2021,49(10):5845
Splicing is catalyzed by the spliceosome, a compositionally dynamic complex assembled stepwise on pre-mRNA. We reveal links between splicing machinery components and the intrinsically disordered ciliopathy protein SANS. Pathogenic mutations in SANS/USH1G lead to Usher syndrome—the most common cause of deaf-blindness. Previously, SANS was shown to function only in the cytosol and primary cilia. Here, we have uncovered molecular links between SANS and pre-mRNA splicing catalyzed by the spliceosome in the nucleus. We show that SANS is found in Cajal bodies and nuclear speckles, where it interacts with components of spliceosomal sub-complexes such as SF3B1 and the large splicing cofactor SON but also with PRPFs and snRNAs related to the tri-snRNP complex. SANS is required for the transfer of tri-snRNPs between Cajal bodies and nuclear speckles for spliceosome assembly and may also participate in snRNP recycling back to Cajal bodies. SANS depletion alters the kinetics of spliceosome assembly, leading to accumulation of complex A. SANS deficiency and USH1G pathogenic mutations affects splicing of genes related to cell proliferation and human Usher syndrome. Thus, we provide the first evidence that splicing dysregulation may participate in the pathophysiology of Usher syndrome. 相似文献
7.
8.
Baran Akagunduz Muhammet Ozer Fatih Ozccek Ali Veysel Kara Sahin Lacn Mustafa
zkaraca Abdulkadir oban Bahadr Suleyman Renad Mammadov Halis Suleyman 《Experimental Animals》2021,70(2):169
Pazopanib is a tyrosine kinase inhibitor that is generally used for the treatment of metastatic renal cell cancer and advanced soft tissue sarcoma. It can cause various degrees of hepatotoxicity. Our study aimed to investigate the effect of taxifolin on pazopanib-induced liver toxicity. A total of 18 rats were divided into three groups: the pazopanib (PP), pazopanib plus taxifolin (TPP), and control (C) group. Taxifolin was administered to the TPP (n=6) group with a dose of 50 mg/kg. Distilled water was orally admnistered to the C (n=6) and PP (n=6) groups as a solvent. Subsequently, pazopanib 200 mg/kg was administered to the TPP and PP groups via the stomach. This procedure was repeated once a day for four weeks. Then, all rats were sacrificed, and their livers were removed. Malondialdehyde (MDA), total glutathione (tGSH), total oxidant status (TOS), and total antioxidant status (TAS) levels were evaluated. MDA and TOS levels were higher in the PP group compared with the levels of the other parameters (P<0.001). tGSH and TAS levels were lower in the PP group than in the TPP and C groups (P<0.001), and the aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) levels were higher. Furthermore, liver tissue damage, including hemorrhage, hydropic degeneration, and necrosis was observed in the PP group. Administration of taxifolin before pazopanib significantly improved degenerative changes. Our study demonstrated that the administration of taxifolin is significantly effective in preventing pazopanib-induced hepatotoxicity in rats. 相似文献
9.
Yildiz Öner-İyidoğan Hikmet Koçak Muhammed Seyidhanoğlu Figen Gürdöl Ahmet Gülçubuk Funda Yildirim Aydin Çevik Müjdat Uysal 《Journal of physiology and biochemistry》2013,69(4):677-686
Fetuin-A is synthesized in the liver and is secreted into the bloodstream. Clinical studies suggest involvement of fetuin-A in metabolic disorders such as visceral obesity, insulin resistance, diabetes, and fatty liver. Curcumin is extracted from the rhizome Curcuma longa and has been shown to possess potent antioxidant, anticarcinogenic, anti-inflammatory, and hypoglycemic properties. In this study, we investigated the effect of curcumin treatment on serum fetuin-A levels as well as hepatic lipids and prooxidant–antioxidant status in rats fed a high-fat diet (HFD). Male Sprague–Dawley rats were divided into six groups. Group 1 was fed control diet (10 % of total calories from fat). Groups 2 and 3 were given curcumin (100 and 400 mg/kg bw/day, respectively ) by gavage for 8 weeks and were fed control diet. Group 4 was fed with HFD (60 % of total calories from fat). Groups 5 and 6 received HFD together with the two doses of curcumin, respectively. Curcumin treatment appeared to be effective in reducing liver triglycerides and serum fetuin-A levels. These findings suggest that the reduction of fetuin-A may contribute to the beneficial effects of curcumin in the pathogenesis of obesity. 相似文献
10.
Ertan Kucuksayan Aysegul Cort Mujgan Timur Evrim Ozdemir Suleyman Gultekin Yucel Prof. Dr. Tomris Ozben 《Journal of cellular biochemistry》2013,114(7):1685-1694
Antioxidants may prevent apoptosis of cancer cells via inhibiting reactive oxygen species (ROS). However, to date no study has been carried out to elucidate the effects of strong antioxidant N‐acetylcysteine (NAC) on Bleomycin induced apoptosis in human testicular cancer (NTERA‐2, NT2) cells. For this reason, we studied the effects of Bleomycin and NAC alone and in combination on apoptotic signaling pathways in NT2 cell line. We determined the cytotoxic effect of bleomycin on NT2 cells and measured apoptosis markers such as Caspase‐3, ‐8, ‐9 activities and Bcl‐2, Bax, Cyt‐c, Annexin V‐FTIC and PI levels in NT2 cells incubated with different agents for 24 h. Early apoptosis was determined using FACS assay. We found half of the lethal dose (LD50) of Bleomycin on NT2 cell viability as 400, 100, and 20 µg/ml after incubations for 24, 48, and 72 h, respectively. Incubation with bleomycin (LD50) and H2O2 for 24 h increased Caspase‐3, ‐8, ‐9 activities, Cyt‐c and Bax levels and decreased Bcl‐2 levels. The concurrent incubation of NT2 cells with bleomycin/H2O2 and NAC (5 mM) for 24 h abolished bleomycin/H2O2‐dependent increases in Caspase‐3, ‐8, ‐9 activities, Bax and Cyt‐c levels and bleomycin/H2O2‐dependent decrease in Bcl‐2 level. Our results indicate that bleomycin/H2O2 induce apoptosis in NT2 cells by activating mitochondrial pathway of apoptosis, while NAC diminishes bleomycin/H2O2 induced apoptosis. We conclude that NAC has antagonistic effects on Bleomycin‐induced apoptosis in NT2 cells and causes resistance to apoptosis which is not a desired effect in eliminating cancer cells. J. Cell. Biochem. 114: 1685–1694, 2013. © 2013 Wiley Periodicals, Inc. 相似文献