全文获取类型
收费全文 | 535篇 |
免费 | 45篇 |
国内免费 | 1篇 |
专业分类
581篇 |
出版年
2023年 | 2篇 |
2022年 | 10篇 |
2021年 | 10篇 |
2020年 | 8篇 |
2019年 | 12篇 |
2018年 | 15篇 |
2017年 | 20篇 |
2016年 | 21篇 |
2015年 | 33篇 |
2014年 | 34篇 |
2013年 | 42篇 |
2012年 | 55篇 |
2011年 | 36篇 |
2010年 | 34篇 |
2009年 | 29篇 |
2008年 | 36篇 |
2007年 | 29篇 |
2006年 | 23篇 |
2005年 | 19篇 |
2004年 | 33篇 |
2003年 | 15篇 |
2002年 | 17篇 |
2001年 | 4篇 |
2000年 | 5篇 |
1999年 | 7篇 |
1998年 | 3篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1995年 | 2篇 |
1994年 | 4篇 |
1993年 | 1篇 |
1992年 | 3篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1980年 | 1篇 |
1979年 | 3篇 |
1977年 | 1篇 |
1976年 | 2篇 |
1972年 | 1篇 |
1969年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有581条查询结果,搜索用时 15 毫秒
1.
Mutational analysis of the RecA protein L1 region identifies this area as a probable part of the co-protease substrate binding site 总被引:3,自引:0,他引:3
Horacio G. Nastri Angelina Guzzo Craig S. Lange Graham C. Walker & Kendall L. Knight 《Molecular microbiology》1997,25(5):967-978
Previous mutational analysis of the L1 region of the RecA protein suggested that Gly-157 and Glu-158 are 'hot-spots' for the occurrence of constitutive LexA co-protease mutants (coprtc ). In the present study, we clearly establish that position 157 is a hot-spot for the occurrence of such mutants, as 12 of 14 and 10 of 14 substitutions result in this phenotype for UmuD and LexA cleavage respectively. The frequency of such mutations at position 158 is somewhat lower, 8 of 13 and 5 of 13 for UmuD and LexA respectively. Comparison of the UmuD vs. LexA co-protease activity for all single mutants with substitutions at positions 154, 155, 156, 157 and 158 (47 in total) reveals that, although there is good agreement among most mutants regarding their ability to cleave both LexA and UmuD, there are two in particular (Glu-154→Asp and Glu-154→Gln) that show a clear preference for cleavage of UmuD. We also show that three second-site mutations that completely suppress coprtc activity toward LexA have little or no effect on the coprtc activity of the primary mutant toward UmuD. In addition, we observe a high frequency of second-site suppressor mutations, suggesting a functional interaction among side-chains in this region. Together, these results support the idea that the L1 region of RecA makes up part of the co-protease substrate-binding site. 相似文献
2.
3.
Angelina Passeri Michael Schmidt Thomas Haffner Victor Wray Siegmund Lang Fritz Wagner 《Applied microbiology and biotechnology》1992,37(3):281-286
Summary During screening for biosurfactants among marine, n-alkane-utilizing bacteria, low- and high-molecular surface-active substances were detected. The marine bacterial strain MM1 was found to synthesize a novel glycolipid that has not so far been cited in the literature. Both 1H, 13C-nuclear magnetic resonance spectroscopic and positive ion fast atom bombardment mass spectrometer studies led to the identification of a glucose lipid consisting of four 3-OH-decanoic acids, which are linked together by ester bonds. The lipophilic moiety is coupled glycosidically with C-1 of glucose. The glucolipid reduced the surface tension from 72 mN/m to 30 mN/m while the minimum interfacial tension towards n-hexadecane was lowered to values smaller than 5 mN/m.
Correspondence to: S. Lang 相似文献
4.
Mark C. Willingham Nancy D. Richert Angelina V. Rutherford 《Experimental cell research》1987,171(2):284-295
Using a monoclonal antibody, we have detected an antigen present in a unique fibrillar structure in the cytoplasm of cultured cells by immunofluorescence. These structures have been identified by transmission electron microscopy and ultrastructural immunocytochemistry as large single paracrystalline arrays of individual filaments morphologically similar to intermediate filaments. The antibody detects these structures in fibroblastic and epithelioid cultured cell lines of mouse, rat, bovine, and human origin but not of avian origin. Only a small percentage of the cells in a culture contains these structures; each cell usually contains only one, although two or more have been observed in a single cell. The structures are elongated vermiform arrays of filaments in the cytoplasm (approximately 0.5 X 3 microns) which have a thread-like or toroidal appearance. Because of this shape, we have named the putative antigen recognized by this antibody "nematin." Double-label experiments showed that these structures had no relationship to tubulin or vimentin. Immunocytochemical localization in human tissues revealed a high concentration of a reactive antigen in the stratum granulosum of skin and in what probably are neuroglial cells in the central nervous system. This monoclonal antibody may detect a novel intermediate filament protein and/or a shared determinant of different intermediate filament proteins. 相似文献
5.
Shen J Pavone A Mikulec C Hensley SC Traner A Chang TK Person MD Fischer SM 《Journal of proteome research》2007,6(1):273-286
Exposure of murine skin to tumor-promoting agents such as 12-O-tetradecanoyl-phorbol-13-acetate (TPA) causes up-regulation of cyclooxygenase-2 (COX-2) and increased prostaglandin (PG) synthesis. Pharmacological inhibition of COX-2 significantly reduces skin tumor development. However, we previously demonstrated that K14.COX-2 transgenic (TG) mice that overexpressed COX-2 in the epidermis were unexpectedly resistant to tumor development under the classical 7,12-dimethylbenz[a]anthracene-TPA protocol. In the present study, we employed a proteomic approach of 2-dimensional gel electrophoresis (2-DE) and mass spectrometry to profile differentially expressed proteins in the epidermis of K14.COX-2 TG and wild-type control mice. Various 2-DE approaches were used to identify the maximum number of differentially expressed proteins: 20 for untreated samples, 3 for acetone-treated samples, and 22 for TPA-treated samples. These proteins include 14-3-3 sigma, numerous actin fragments, actin filament related proteins cofilin-1 and destrin, galectin-3, galectin-7, prohibitin, S100A6, S100A9, and many others. The differential expression of galectin-3, galectin-7, S100A9 was validated by Western blot analysis and/or immunohistochemical analysis. The current data suggest that some of the differentially expressed proteins might increase apoptosis and cell cycle arrest, which, in turn, may provide insight into the role of COX-2 in skin tumorigenesis. 相似文献
6.
7.
Lorena Esposito-Bauer Tobias Saam Iman Ghodrati Jaroslav Pelisek Peter Heider Matthias Bauer Petra Wolf Angelina Bockelbrink Regina Feurer Dominik Sepp Claudia Winkler Peter Zepper Tobias Boeckh-Behrens Matthias Riemenschneider Bernhard Hemmer Holger Poppert 《PloS one》2013,8(7)
Purpose
The aim of this study was to investigate prospectively whether MRI plaque imaging can identify patients with asymptomatic carotid artery stenosis who have an increased risk for future cerebral events. MRI plaque imaging allows categorization of carotid stenosis into different lesion types (I–VIII). Within these lesion types, lesion types IV–V and VI are regarded as rupture-prone plaques, whereas the other lesion types represent stable ones.Methods
Eighty-three consecutive patients (45 male (54.2%); age 54–88 years (mean 73.2 years)) presenting with an asymptomatic carotid stenosis of 50–99% according to ECST-criteria were recruited. Patients were imaged with a 1.5-T scanner. T1-, T2-, time-of-flight-, and proton-density weighted studies were performed. The carotid plaques were classified as lesion type I–VIII. Clinical endpoints were ischemic stroke, TIA or amaurosis fugax. Survival analysis and log rank test were used to ascertain statistical significance.Results
Six out of 83 patients (7.2%) were excluded: 4 patients had insufficient MR image quality; 1 patient was lost-to-follow-up; 1 patient died shortly after the baseline MRI plaque imaging. The following results were obtained by analyzing the remaining 77 patients. The mean time of follow-up was 41.1 months.During follow-up, n = 9 (11.7%) ipsilateral ischemic cerebrovascular events occurred. Only patients presenting with the high-risk lesion types IV–V and VI developed an ipsilateral cerebrovascular event versus none of the patients presenting with the stable lesion types III, VII, and VIII (n = 9 (11.7%) vs. n = 0 (0%) during follow-up). Event-free survival was higher among patients with the MRI-defined stable lesion types (III, VII, and VIII) than in patients with the high-risk lesion types (IV–V and VI) (log rank test P<0.0001).Conclusions
MRI plaque imaging has the potential to identify patients with asymptomatic carotid stenosis who are particularly at risk of developing future cerebral ischemia. MRI could improve selection criteria for invasive therapy in the future. 相似文献8.
K. H. Yiu F. R. de Graaf J. E. van Velzen N. A. Marsan C. J. Roos M. K. de Bie H. F. Tse E. E. van der Wall M. J. Schalij J. J. Bax J. D. Schuijf J. W. Jukema 《Netherlands heart journal》2013,21(7-8):347-353
Purpose
The coronary calcium score (CCS) predicts significant coronary artery disease (CAD) in the general population. While moderate chronic kidney disease (CKD) is associated with high CCS, the use of CCS to predict significant CAD in these patients is unknown.Methods
A total of 704 patients underwent computed tomography coronary angiography for the assessment of CCS and CAD. Sixty-nine (10 %) patients had moderate CKD, defined by an estimated glomerular filtration rate (eGFR) between 30 and 59 mL/min/1.73m2, and the remaining patients were considered to be without significant CKD (eGFR?≥?60 mL/min/1.73m2).Results
Patients with moderate CKD were older, had a higher CCS, and a higher prevalence of obstructive CAD than patients without significant CKD. Receiver-operator curve analysis showed that CCS predicted the presence of obstructive CAD in both patients with moderate CKD and those without significant CKD. In patients with moderate CKD, the optimal cut-off value of CCS to diagnose obstructive CAD was 140 (sensitivity 73 % and specificity of 70 %), and is 2.8 fold higher than in patients without significant CKD (cut-off value?=?50; sensitivity 75 % and specificity 75 %).Conclusion
The present results demonstrate that CCS can predict obstructive CAD in patients with moderate CKD, although the optimal cut-off value is higher than in patients without significant CKD. 相似文献9.
Felix Moerman Angelina Arquint Stefanie Merkli Andreas Wagner Florian Altermatt Emanuel A. Fronhofer 《Evolution; international journal of organic evolution》2020,74(3):573-586
Abiotic stress is a major force of selection that organisms are constantly facing. While the evolutionary effects of various stressors have been broadly studied, it is only more recently that the relevance of interactions between evolution and underlying ecological conditions, that is, eco-evolutionary feedbacks, have been highlighted. Here, we experimentally investigated how populations adapt to pH-stress under high population densities. Using the protist species Tetrahymena thermophila, we studied how four different genotypes evolved in response to stressfully low pH conditions and high population densities. We found that genotypes underwent evolutionary changes, some shifting up and others shifting down their intrinsic rates of increase (r0). Overall, evolution at low pH led to the convergence of r0 and intraspecific competitive ability (α) across the four genotypes. Given the strong correlation between r0 and α, we argue that this convergence was a consequence of selection for increased density-dependent fitness at low pH under the experienced high density conditions. Increased density-dependent fitness was either attained through increase in r0, or decrease of α, depending on the genetic background. In conclusion, we show that demography can influence the direction of evolution under abiotic stress. 相似文献
10.
Milana Trifunović-Momčilov Danijela Paunović Snežana Milošević Marija Marković Slađana Jevremović Ivana Č Dragićević Angelina Subotić 《The Annals of applied biology》2020,177(1):74-89
Common centaury (Centaurium erythraea Rafn.) is a plant species that can inhabit saline soils. It is known as a plant with high spontaneous regeneration potential in vitro. In the present work we evaluated shoots and roots salinity tolerance of non-transformed and three AtCKX transgenic centaury lines to graded NaCl concentrations (0, 50, 100, 150, 200 mM) in vitro. Overexpression of AtCKX genes in transgenic centaury plants resulted in an altered cytokinins (CKs) profile leading to a decline of bioactive CK levels and, at the same time, increased contents of storage CK forms, inactive CK forms and/or CK nucleotides. Significant increment of fresh shoot weight was obtained in shoots of non-transformed and AtCKX1 transgenic line only on medium supplemented with 50 mM NaCl. However two analysed AtCKX2 transgenic lines reduced shoot growth at all NaCl concentrations. In general, centaury roots showed higher tolerance to salinity than shoots. Non-transformed and AtCKX1 transgenic lines tolerated up to 100 mM NaCl without change in frequency of regeneration and number of regenerated plants. Roots of two analysed AtCKX2 transgenic lines showed different regeneration potential under salt stress. Regeneration of transgenic AtCKX2-26 shoots even at 200 mM NaCl was recorded. Salinity stress response of centaury shoots and roots was also evaluated at biochemical level. Free proline, malondialdehyde and hydrogen peroxide content as well as antioxidative enzymes activities were investigated in shoots and roots after 1, 2, 4 and 8 weeks. In general, adition of NaCl in culture medium elevated all biochemical parameters in centaury shoots and in roots. Considering that all analysed AtCKX transgenic centaury lines showed altered salt tolerance to graded NaCl concentrations in vitro it can be assumed that CKs might be involved in plant defence to salt stress conditions. 相似文献