全文获取类型
收费全文 | 336篇 |
免费 | 30篇 |
专业分类
366篇 |
出版年
2021年 | 14篇 |
2020年 | 2篇 |
2019年 | 4篇 |
2018年 | 3篇 |
2017年 | 5篇 |
2016年 | 6篇 |
2015年 | 15篇 |
2014年 | 8篇 |
2013年 | 14篇 |
2012年 | 19篇 |
2011年 | 21篇 |
2010年 | 15篇 |
2009年 | 13篇 |
2008年 | 20篇 |
2007年 | 16篇 |
2006年 | 23篇 |
2005年 | 16篇 |
2004年 | 11篇 |
2003年 | 14篇 |
2002年 | 21篇 |
2001年 | 6篇 |
1999年 | 4篇 |
1998年 | 4篇 |
1997年 | 2篇 |
1996年 | 4篇 |
1995年 | 4篇 |
1994年 | 10篇 |
1993年 | 2篇 |
1992年 | 4篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1989年 | 2篇 |
1988年 | 2篇 |
1987年 | 6篇 |
1986年 | 4篇 |
1985年 | 2篇 |
1984年 | 4篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1981年 | 2篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1977年 | 5篇 |
1976年 | 4篇 |
1975年 | 3篇 |
1974年 | 7篇 |
1973年 | 4篇 |
1972年 | 1篇 |
1968年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有366条查询结果,搜索用时 15 毫秒
91.
92.
93.
94.
95.
The Escherichia coli multidrug transporter MdfA contains a membrane-embedded charged residue (Glu-26) that was shown to play an important role in substrate recognition. To identify additional determinants of multidrug recognition we isolated 58 intragenic second-site mutations that restored the function of inactive MdfA E26X mutants. In addition, two single-site mutations that enhanced the activity of wild-type MdfA were identified. Most of the mutations were found in two regions, the cytoplasmic half of transmembrane segments (TMs) 4, 5, and 6 (cluster 1) and the periplasmic half of TM 1 and 2 (cluster 2). The identified residues were mutated to cysteines in the background of a functional cysteine-less MdfA, and substrate protection against alkylation was analyzed. The results support the suggestion that the two clusters are involved in substrate recognition. Using inverted membrane vesicles we observed that a proton electrochemical gradient (Deltamicro(H(+)), inside positive and acidic) enhanced the substrate-protective effect in the cytoplasmic region, whereas it largely reduced this effect in the periplasmic side of MdfA. Therefore, we propose that substrates interact with two sites in MdfA, one in the cytoplasmic leaflet of the membrane and the other in the periplasmic leaflet. Theoretically, these domains could constitute a large part of the multidrug pathway through MdfA. 相似文献
96.
Elaad E 《Applied psychophysiology and biofeedback》2011,36(3):159-171
The accuracy of the Concealed Information Test in correct classification of informed guilty and informed innocent participants
was assessed when the explicitness of the obtained information varied. For these purposes, a mock crime procedure was employed
and participants were randomly assigned to six conditions formed by combinations of two levels of the state of guilt (guilty
and innocent) and three levels of information completeness (exact, indicative, non-specific). As expected, informed guilty
participants were more accurately detected than informed innocents. It was further found that when the gathered information
was less explicit, detection efficiency decreased. Theoretical and practical implications of the present results are discussed. 相似文献
97.
Several methods have been proposed for detecting insertion/deletions (indels) from chromatograms generated by Sanger sequencing. However, most such methods are unsuitable when the mutated and normal variants occur at unequal ratios, such as is expected to be the case in cancer, with organellar DNA or with alternatively spliced RNAs. In addition, the current methods do not provide robust estimates of the statistical confidence of their results, and the sensitivity of this approach has not been rigorously evaluated. Here, we present CHILD, a tool specifically designed for indel detection in mixtures where one variant is rare. CHILD makes use of standard sequence alignment statistics to evaluate the significance of the results. The sensitivity of CHILD was tested by sequencing controlled mixtures of deleted and undeleted plasmids at various ratios. Our results indicate that CHILD can identify deleted molecules present as just 5% of the mixture. Notably, the results were plasmid/primer-specific; for some primers and/or plasmids, the deleted molecule was only detected when it comprised 10% or more of the mixture. The false positive rate was estimated to be lower than 0.4%. CHILD was implemented as a user-oriented web site, providing a sensitive and experimentally validated method for the detection of rare indel-carrying molecules in common Sanger sequence reads. 相似文献
98.
Victor Yashunsky Leorah Kharilker Efrat Zlotkin-Rivkin David Rund Naomi Melamed-Book Eitan Erez Zahavi Eran Perlson Silvana Mercone Michael Golosovsky Dan Davidov Benjamin Aroeti 《PloS one》2013,8(10)
Enteropathogenic Escherichia coli (EPEC) is an important, generally non-invasive, bacterial pathogen that causes diarrhea in humans. The microbe infects mainly the enterocytes of the small intestine. Here we have applied our newly developed infrared surface plasmon resonance (IR-SPR) spectroscopy approach to study how EPEC infection affects epithelial host cells. The IR-SPR experiments showed that EPEC infection results in a robust reduction in the refractive index of the infected cells. Assisted by confocal and total internal reflection microscopy, we discovered that the microbe dilates the intercellular gaps and induces the appearance of fluid-phase-filled pinocytic vesicles in the lower basolateral regions of the host epithelial cells. Partial cell detachment from the underlying substratum was also observed. Finally, the waveguide mode observed by our IR-SPR analyses showed that EPEC infection decreases the host cell''s height to some extent. Together, these observations reveal novel impacts of the pathogen on the host cell architecture and endocytic functions. We suggest that these changes may induce the infiltration of a watery environment into the host cell, and potentially lead to failure of the epithelium barrier functions. Our findings also indicate the great potential of the label-free IR-SPR approach to study the dynamics of host-pathogen interactions with high spatiotemporal sensitivity. 相似文献
99.
Ehud Ohana Eitan Hoch Chen Keasar Taiho Kambe Ofer Yifrach Michal Hershfinkel Israel Sekler 《The Journal of biological chemistry》2009,284(26):17677-17686
Vesicular zinc transporters (ZnTs) play a critical role in regulating Zn2+ homeostasis in various cellular compartments and are linked to major diseases ranging from Alzheimer disease to diabetes. Despite their importance, the intracellular localization of ZnTs poses a major challenge for establishing the mechanisms by which they function and the identity of their ion binding sites. Here, we combine fluorescence-based functional analysis and structural modeling aimed at elucidating these functional aspects. Expression of ZnT5 was followed by both accelerated removal of Zn2+ from the cytoplasm and its increased vesicular sequestration. Further, activity of this zinc transport was coupled to alkalinization of the trans-Golgi network. Finally, structural modeling of ZnT5, based on the x-ray structure of the bacterial metal transporter YiiP, identified four residues that can potentially form the zinc binding site on ZnT5. Consistent with this model, replacement of these residues, Asp599 and His451, with alanine was sufficient to block Zn2+ transport. These findings indicate, for the first time, that Zn2+ transport mediated by a mammalian ZnT is catalyzed by H+/Zn2+ exchange and identify the zinc binding site of ZnT proteins essential for zinc transport. 相似文献
100.