全文获取类型
收费全文 | 698篇 |
免费 | 52篇 |
专业分类
750篇 |
出版年
2023年 | 3篇 |
2022年 | 4篇 |
2021年 | 14篇 |
2020年 | 5篇 |
2019年 | 14篇 |
2018年 | 15篇 |
2017年 | 9篇 |
2016年 | 21篇 |
2015年 | 32篇 |
2014年 | 39篇 |
2013年 | 50篇 |
2012年 | 49篇 |
2011年 | 43篇 |
2010年 | 29篇 |
2009年 | 29篇 |
2008年 | 40篇 |
2007年 | 44篇 |
2006年 | 46篇 |
2005年 | 39篇 |
2004年 | 34篇 |
2003年 | 35篇 |
2002年 | 25篇 |
2001年 | 14篇 |
2000年 | 9篇 |
1999年 | 14篇 |
1998年 | 11篇 |
1997年 | 6篇 |
1996年 | 8篇 |
1995年 | 5篇 |
1994年 | 3篇 |
1991年 | 7篇 |
1990年 | 9篇 |
1989年 | 3篇 |
1988年 | 7篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 5篇 |
1984年 | 2篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1980年 | 3篇 |
1979年 | 3篇 |
1978年 | 4篇 |
1975年 | 1篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1969年 | 2篇 |
1966年 | 1篇 |
1962年 | 1篇 |
排序方式: 共有750条查询结果,搜索用时 10 毫秒
21.
Saurabh Sudha Dhiman Dayanand Kalyani Sujit Sadashiv Jagtap Jung-Rim Haw Yun Chan Kang Jung-Kul Lee 《Applied microbiology and biotechnology》2013,97(3):1081-1091
Enhanced catalytic activities of different lignocellulases were obtained from Armillaria gemina under statistically optimized parameters using a jar fermenter. This strain showed maximum xylanase, endoglucanase, cellobiohydrolase, and β-glucosidase activities of 1,270, 146, 34, and 15 U mL?1, respectively. Purified A. gemina xylanase (AgXyl) has the highest catalytic efficiency (k cat/K m?=?1,440 mg?mL?1?s?1) ever reported for any fungal xylanase, highlighting the significance of the current study. We covalently immobilized the crude xylanase preparation onto functionalized silicon oxide nanoparticles, achieving 117 % immobilization efficiency. Further immobilization caused a shift in the optimal pH and temperature, along with a fourfold improvement in the half-life of crude AgXyl. Immobilized AgXyl gave 37.8 % higher production of xylooligosaccharides compared to free enzyme. After 17 cycles, the immobilized enzyme retained 92 % of the original activity, demonstrating its potential for the synthesis of xylooligosaccharides in industrial applications. 相似文献
22.
23.
Poulami Das Akanksha Bansal Sudha Narayan Rao Kedar Deodhar Umesh Mahantshetty Shyam K. Shrivastava Karthikeyan Sivaraman Rita Mulherkar 《PloS one》2016,11(11)
There are very few reports that describe the mutational landscape of cervical cancer, one of the leading cancers in Indian women. The aim of the present study was to investigate the somatic mutations that occur in cervical cancer. Whole exome sequencing of 10 treatment naïve tumour biopsies with matched blood samples, from a cohort of Indian patients with locally advanced disease, was performed. The data revealed missense mutations across 1282 genes, out of 1831 genes harbouring somatic mutations. These missense mutations (nonsynonymous + stop-gained) when compared with pre-existing mutations in the COSMIC database showed that 272 mutations in 250 genes were already reported although from cancers other than cervical cancer. More than 1000 novel somatic variations were obtained in matched tumour samples. Pathways / genes that are frequently mutated in various other cancers were found to be mutated in cervical cancers. A significant enrichment of somatic mutations in the MAPK pathway was observed, some of which could be potentially targetable. This is the first report of whole exome sequencing of well annotated cervical cancer samples from Indian women and helps identify trends in mutation profiles that are found in an Indian cohort of cervical cancer. 相似文献
24.
B. Sudha Kalyani P.S. Krishna K. Sreenivasulu 《Saudi Journal of Biological Sciences》2019,26(7):1655-1660
Actinobacteria, which are the prolific producers of antibiotics and significant suppliers to the pharmaceutical industry, can produce a wide variety of bioactive metabolites. An actinomycete strain designated NLKPB45 was isolated from mangrove soils samples of Nellore coastal regions Andhra Pradesh and assessed for antibiotic production and activity against pathogenic bacteria. From a total of 9 mangrove soil samples, 143 acinomycetes were isolated. Among the isolated them 6 actinomycetes strains showed potential antibacterial activity against at two tested pathogens gram positive and gram negative bacteria E. coli and S. aureus. The potent strain NLKPB45 was identified by 16S gene isolation and sequencing to the Streptomyces genus. The ethyl acetate extracts also as shown excellent antimicrobial activity against Salmonella sp., staphylococcus aureus, E. coli, and B. subtilus were detected in both the supernatant extract samples from fermentations of culture NLKPB45. The anticancer activity of extracts in the HeLa with IC50 value of 37.1924 μg/ml, MCF-7 IC50 value of 40.9177 μg/ml and HT 29 IC50 value of 43.3758 μg/ml. 相似文献
25.
Beta-arrestin and Mdm2 mediate IGF-1 receptor-stimulated ERK activation and cell cycle progression 总被引:1,自引:0,他引:1
Girnita L Shenoy SK Sehat B Vasilcanu R Vasilcanu D Girnita A Lefkowitz RJ Larsson O 《The Journal of biological chemistry》2007,282(15):11329-11338
Beta-arrestin1, which regulates many aspects of seven transmembrane receptor (7TMR) biology, has also been shown to serve as an adaptor, which brings Mdm2, an E3 ubiquitin ligase to the insulin-like growth factor-1 receptor (IGF-1R), leading to its proteasome-dependent destruction. Here we demonstrate that IGF-1R stimulation also leads to ubiquitination of beta-arrestin1, which regulates vesicular trafficking and activation of ERK1/2. This beta-arrestin1-dependent ERK activity can occur even when the classical tyrosine kinase signaling is impaired. siRNA-mediated suppression of beta-arrestin1 in human melanoma cells ablates IGF-1-stimulated ERK and prolongs the G1 phase of the cell cycle. These data suggest that beta-arrestin-dependent ERK signaling by the IGF-1R regulates cell cycle progression and may thus be an important regulator of the growth of normal and malignant cells. 相似文献
26.
List EO Berryman DE Palmer AJ Qiu L Sankaran S Kohn DT Kelder B Okada S Kopchick JJ 《Proteomics》2007,7(7):1140-1149
In this study, proteomic analysis was performed on the skin of C57BL/6J mice with type 2 diabetes and compared to nondiabetic controls. To induce obesity and subsequent diabetes, mice were placed on a high-fat diet for 16 wk. After 16 wk, both diabetic and nondiabetic control mice were sacrificed and their skin removed for analysis. Following 2-DE, proteomic profiles from the skin samples were quantified using PDQuest software. Out of more than 1000 distinct protein spots, 28 were shown to be significantly altered with 6 being decreased and 22 increased in the diabetic state compared to controls. The 28 protein spots were removed from the gels and analyzed by MALDI-TOF and MS/MS analyses. Protein identifications revealed that 17 of the 28 proteins were involved in energy metabolism (60.7% of changes observed). Collectively, none of the significantly altered proteins had been shown previously to be altered in diabetic skin. This study not only helps to identify proteins found in skin samples of obese mice with type 2 diabetes, but also shows that skin biopsies coupled with proteomic analysis may be useful as a noninvasive method for the diagnosis of hyperinsulinemia and diabetes. 相似文献
27.
Pierre-Yves Jean-Charles Vishwaesh Rajiv Subhodeep Sarker Sangoh Han Yushi Bai Ali Masoudi Sudha K. Shenoy 《The Journal of biological chemistry》2022,298(5)
Arrestins and their yeast homologs, arrestin-related trafficking adaptors (ARTs), share a stretch of 29 amino acids called the ART motif. However, the functionality of that motif is unknown. We now report that deleting this motif prevents agonist-induced ubiquitination of β-arrestin2 (β-arr2) and blocks its association with activated G protein–coupled receptors (GPCRs). Within the ART motif, we have identified a conserved phenylalanine residue, Phe116, that is critical for the formation of β-arr2–GPCR complexes. β-arr2 Phe116Ala mutant has negligible effect on blunting β2-adrenergic receptor–induced cAMP generation unlike β-arr2, which promotes rapid desensitization. Furthermore, available structures for inactive and inositol hexakisphosphate 6–activated forms of bovine β-arr2 revealed that Phe116 is ensconced in a hydrophobic pocket, whereas the adjacent Phe117 and Phe118 residues are not. Mutagenesis of Phe117 and Phe118, but not Phe116, preserves GPCR interaction of β-arr2. Surprisingly, Phe116 is dispensable for the association of β-arr2 with its non-GPCR partners. β-arr2 Phe116Ala mutant presents a significantly reduced protein half-life compared with β-arr2 and undergoes constitutive Lys-48-linked polyubiquitination, which tags proteins for proteasomal degradation. We also found that Phe116 is critical for agonist-dependent β-arr2 ubiquitination with Lys-63-polyubiquitin linkages that are known mediators of protein scaffolding and signal transduction. Finally, we have shown that β-arr2 Phe116Ala interaction with activated β2-adrenergic receptor can be rescued with an in-frame fusion of ubiquitin. Taken together, we conclude that Phe116 preserves structural stability of β-arr2, regulates the formation of β-arr2–GPCR complexes that inhibit G protein signaling, and promotes subsequent ubiquitin-dependent β-arr2 localization and trafficking. 相似文献
28.
Chang-An Yu Hua Tian Li Zhang Kai-Ping Deng Sudha K. Shenoy Linda Yu Di Xia Hoeon Kim Johann Deisenhofer 《Journal of bioenergetics and biomembranes》1999,31(3):191-200
The mitochondrial cytochrome bc
1 complex is a multifunctional membrane protein complex. Itcatalyzes electron transfer, proton translocation, peptide processing, and superoxide generation.Crystal structure data at 2.9 Å resolution not only establishes the location of the redox centersand inhibitor binding sites, but also suggests a movement of the head domain of the iron–sulfurprotein (ISP) during bc
1 catalysis and inhibition of peptide-processing activity during complexmaturation. The functional importance of the movement of extramembrane (head) domain ofISP in the bc
1 complex is confirmed by analysis of the Rhodobacter sphaeroides bc
1 complexmutants with increased rigidity in the ISP neck and by the determination of rate constants foracid/base-induced intramolecular electron transfer between [2Fe–2S] and heme c
1 in nativeand inhibitor-loaded beef complexes. The peptide-processing activity is activated in bovineheart mitochondrial bc
1 complex by nonionic detergent at concentrations that inactivate electrontransfer activity. This peptide-processing activity is shown to be associated with subunits Iand II by cloning, overexpression and in vitro reconstitution. The superoxide-generation siteof the cytochrome bc
1 complex is located at reduced b
L and Q–. The reaction is membranepotential-, and cytochrome c-dependent. 相似文献
29.
Cecropin A (1-8)-Melittin (1-18) is a synthetic cecropin A-melittin hybrid peptide with leishmanicidal activity. The primary sequence of the peptide is as follows: KWKLPKKIGIGAVLKVLTTGLPALIS-NH2. 1H and 13C 2D NMR techniques were used to deduce the conformational parameters of chemical shift, 3JNHalpha coupling constants, temperature coefficients of NH chemical shifts and the pattern of intra and inter-residue nOe's. NMR studies were carried out in water (pH 6.0) and hexafluoroacetone (HFA). The peptide was found in a beta-pleated structure in water, and in HFA it adopts a right-handed alpha-helix conformation. Solution structures generated using restrained molecular dynamics simulations were refined by Mardigras to R factors ranging from 0.5 to 0.6. 相似文献
30.