全文获取类型
收费全文 | 325篇 |
免费 | 41篇 |
出版年
2018年 | 6篇 |
2017年 | 3篇 |
2016年 | 2篇 |
2015年 | 12篇 |
2014年 | 19篇 |
2013年 | 16篇 |
2012年 | 10篇 |
2011年 | 16篇 |
2010年 | 20篇 |
2009年 | 13篇 |
2008年 | 15篇 |
2007年 | 15篇 |
2006年 | 14篇 |
2005年 | 16篇 |
2004年 | 19篇 |
2003年 | 8篇 |
2002年 | 7篇 |
2001年 | 10篇 |
2000年 | 13篇 |
1999年 | 10篇 |
1998年 | 14篇 |
1997年 | 3篇 |
1996年 | 7篇 |
1995年 | 6篇 |
1994年 | 6篇 |
1993年 | 5篇 |
1992年 | 4篇 |
1991年 | 2篇 |
1990年 | 4篇 |
1989年 | 5篇 |
1988年 | 6篇 |
1987年 | 2篇 |
1986年 | 4篇 |
1985年 | 2篇 |
1984年 | 4篇 |
1983年 | 2篇 |
1981年 | 5篇 |
1977年 | 2篇 |
1974年 | 2篇 |
1972年 | 3篇 |
1917年 | 2篇 |
1914年 | 2篇 |
1912年 | 2篇 |
1910年 | 6篇 |
1909年 | 1篇 |
1908年 | 3篇 |
1907年 | 5篇 |
1906年 | 1篇 |
1905年 | 1篇 |
1904年 | 1篇 |
排序方式: 共有366条查询结果,搜索用时 15 毫秒
91.
Electron microscopic structure of agrin and mapping of its binding site in laminin-1. 总被引:7,自引:0,他引:7
下载免费PDF全文
![点击此处可从《The EMBO journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
A J Denzer T Schulthess C Fauser B Schumacher R A Kammerer J Engel M A Ruegg 《The EMBO journal》1998,17(2):335-343
Agrin is a large, multidomain heparan sulfate proteoglycan that is associated with basement membranes of several tissues. Particular splice variants of agrin are essential for the formation of synaptic structures at the neuromuscular junction. The binding of agrin to laminin appears to be required for its localization to synaptic basal lamina and other basement membranes. Here, electron microscopy was used to determine the structure of agrin and to localize its binding site in laminin-1. Agrin appears as an approximately 95 nm long particle that consists of a globular, N-terminal laminin-binding domain, a central rod predominantly formed by the follistatin-like domains and three globular, C-terminal laminin G-like domains. In a few cases, heparan sulfate glycosaminoglycan chains were seen emerging from the central portion of the core protein. Moreover, we show that agrin binds to the central region of the three-stranded, coiled-coil oligomerization domain in the long arm of laminin-1, which mediates subunit assembly of the native laminin molecule. In summary, our data show for the first time a protein-protein interaction of the extracellular matrix that involves a coiled-coil domain, and they assign a novel role to this domain of laminin-1. Based on this, we propose that agrin associates with basal lamina in a polarized way. 相似文献
92.
A distinct 14 residue site triggers coiled-coil formation in cortexillin I. 总被引:7,自引:1,他引:6
下载免费PDF全文
![点击此处可从《The EMBO journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
M O Steinmetz A Stock T Schulthess R Landwehr A Lustig J Faix G Gerisch U Aebi R A Kammerer 《The EMBO journal》1998,17(7):1883-1891
We have investigated the process of the assembly of the Dictyostelium discoideum cortexillin I oligomerization domain (Ir) into a tightly packed, two-stranded, parallel coiled-coil structure using a variety of recombinant polypeptide chain fragments. The structures of these Ir fragments were analyzed by circular dichroism spectroscopy, analytical ultracentrifugation and electron microscopy. Deletion mapping identified a distinct 14 residue site within the Ir coiled coil, Arg311-Asp324, which was absolutely necessary for dimer formation, indicating that heptad repeats alone are not sufficient for stable coiled-coil formation. Moreover, deletion of the six N-terminal heptad repeats of Ir led to the formation of a four- rather than a two-helix structure, suggesting that the full-length cortexillin I coiled-coil domain behaves as a cooperative folding unit. Most interestingly, a 16 residue peptide containing the distinct coiled-coil 'trigger' site Arg311-Asp324 yielded approximately 30% helix formation as monomer, in aqueous solution. pH titration and NaCl screening experiments revealed that the peptide's helicity depends strongly on pH and ionic strength, indicating that electrostatic interactions by charged side chains within the peptide are critical in stabilizing its monomer helix. Taken together, these findings demonstrate that Arg311-Asp324 behaves as an autonomous helical folding unit and that this distinct Ir segment controls the process of coiled-coil formation of cortexillin I. 相似文献
93.
Microsatellite variation in Drosophila melanogaster and Drosophila simulans: a reciprocal test of the ascertainment bias hypothesis 总被引:2,自引:1,他引:1
Interspecific comparisons of microsatellite loci have repeatedly shown that
the loci are longer and more variable in the species from which they are
derived (the focal species) than are homologous loci in other (nonfocal)
species. There is debate as to whether this is due to directional evolution
or to an ascertainment bias during the cloning and locus selection
processes. This study tests these hypotheses by performing a reciprocal
study. Eighteen perfect dinucleotide microsatellite loci identified from a
Drosophila simulans library screen and 18 previously identified in an
identical Drosophila melanogaster library screen were used to survey
natural populations of each species. No difference between focal and
nonfocal species was observed for mean PCR fragment length. However,
heterozygosity and number of alleles were significantly higher in the focal
species than in the nonfocal species. The most common allele in the
Zimbabwe population of both species was sequenced for 31 of the 36 loci.
The length of the longest stretch of perfect repeat units is, on average,
longer in the focal species than in the non-focal species. There is a
positive correlation between the length of the longest stretch of perfect
repeats and heterozygosity. The difference in heterozygosity can thus be
explained by a reduction in the length of the longest stretch of perfect
repeats in the nonfocal species. Furthermore, flanking-sequence length
difference was noted between the two species at 58% of the loci sequenced.
These data do not support the predictions of the directional-evolution
hypothesis; however, consistent with the ascertainment bias hypothesis, the
lower variability in nonfocal species is an artifact of the microsatellite
cloning and isolation process. Our results also suggest that the magnitude
of ascertainment bias for repeat unit length is a function of the
microsatellite size distribution in the genomes of different species.
相似文献
94.
Prospects for estimating nucleotide divergence with RAPDs 总被引:11,自引:0,他引:11
The technique of random amplification of polymorphic DNA (RAPD), which is
simply polymerase chain reaction (PCR) amplification of genomic DNA by a
single short oligonucleotide primer, produces complex patterns of anonymous
polymorphic DNA fragments. The information provided by these banding
patterns has proved to be of great utility for mapping and for verification
of identity of bacterial strains. Here we consider whether the degree of
similarity of the banding patterns can be used to estimate nucleotide
diversity and nucleotide divergence. With haploid data, fragments generated
by RAPD-PCR can be treated in a fashion very similar to that for
restriction-fragment data. Amplification of diploid samples, on the other
hand, requires consideration of the fact that presence of a band is
dominant to absence of the band. After describing a method for estimating
nucleotide divergence on the basis of diploid samples, we summarize the
restrictions and criteria that must be met when RAPD data are used for
estimating population genetic parameters.
相似文献
95.
96.
97.
98.
Liebich HM Müller-Hagedorn S Bacher M Scheel-Walter HG Lu X Frickenschmidt A Kammerer B Kim KR Gérard H 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2005,814(2):275-283
Modified nucleosides have been characterized as tumor markers for a number of malignant diseases. In order to use these markers in children, the age-dependence of the nucleoside levels in healthy children has to be established and taken into account in diagnostic decisions. In this study, the levels of 12 normal and modified nucleosides in urine of 166 healthy children and adolescents with an age between 1 day and 19 years are determined by reversed-phase HPLC, and age-dependent reference ranges are defined. The urinary nucleoside concentrations are related to the creatinine concentrations, which allows the use of randomly collected urine samples. All nucleoside levels in urine of children decrease with age, most pronounced during the first 4 years of life, and the age-dependence of the reference values of the individual nucleosides can be approximated by a mathematical function y = b(0) + b(1) (1/x) with the regression coefficients b(0) and b(1,) the nucleoside levels y and the age x between 1 year and 19 years. In the very young children, the shifts in the nucleoside concentrations are more differentiated. Starting with low levels on the first day of life, the concentrations of all studied nucleosides rise up to an age of 1-2 months, when they reach their absolute maximum for all age periods, and then decrease. 相似文献
99.
BACKGROUND/AIMS: The Tobago Afro-Caribbean population is a valuable resource for studying the genetics of diseases that show significant differences in prevalence between populations of African descent and populations of other ancestries. Empirical confirmation of low European and Native American admixture may help in clarifying the ethnic variation in risk for such diseases. We hypothesize that the degree of European and Native American admixture in the Tobago population is low. METHODS: Admixture was estimated in a random sample of 220 men, from a population-based prostate cancer screening survey of 3,082 Tobago males, aged 40 to 79 years. We used a set of six autosomal markers with large allele frequency differences between the major ethnic populations involved in the admixture process, Europeans, Native Americans and West Africans. RESULTS: The ancestral proportions of Tobago population are estimated as 94.0+/-1.2% African, 4.6+/-3.4% European and 1.4+/-3.6% Native American. CONCLUSIONS: We conclude that Tobago Afro-Caribbean men are predominantly of West African ancestry, with minimal European and Native American admixture. The Tobago population, thus, may carry a higher burden of high-risk alleles of African origin for certain diseases than the more admixed African-American population. Conversely, this population may benefit from a higher prevalence of protective alleles of African origin. 相似文献
100.
Steinmetz MO Kammerer RA Jahnke W Goldie KN Lustig A van Oostrum J 《The EMBO journal》2000,19(4):572-580
Oncoprotein 18/stathmin (Op18), a regulator of microtubule dynamics, was recombinantly expressed and its structure and function analysed. We report that Op18 by itself can fold into a flexible and extended alpha-helix, which is in equilibrium with a less ordered structure. In complex with tubulin, however, all except the last seven C-terminal residues of Op18 are tightly bound to tubulin. Digital image analysis of Op18:tubulin electron micrographs revealed that the complex consists of two longitudinally aligned alpha/beta-tubulin heterodimers. The appearance of the complex was that of a kinked protofilament-like structure with a flat and a ribbed side. Deletion mapping of Op18 further demonstrated that (i) the function of the N-terminal part of the molecule is to 'cap' tubulin subunits to ensure the specificity of the complex and (ii) the complete C-terminal alpha-helical domain of Op18 is necessary and sufficient for stable Op18:tubulin complex formation. Together, our results suggest that besides sequestering tubulin, the structural features of Op18 enable the protein specifically to recognize microtubule ends to trigger catastrophes. 相似文献