全文获取类型
收费全文 | 254篇 |
免费 | 18篇 |
出版年
2022年 | 1篇 |
2021年 | 1篇 |
2019年 | 1篇 |
2018年 | 2篇 |
2017年 | 4篇 |
2016年 | 4篇 |
2015年 | 14篇 |
2014年 | 10篇 |
2013年 | 6篇 |
2012年 | 14篇 |
2011年 | 9篇 |
2010年 | 11篇 |
2009年 | 7篇 |
2008年 | 6篇 |
2007年 | 10篇 |
2006年 | 13篇 |
2005年 | 10篇 |
2004年 | 8篇 |
2003年 | 12篇 |
2002年 | 11篇 |
2001年 | 9篇 |
2000年 | 9篇 |
1999年 | 9篇 |
1998年 | 10篇 |
1997年 | 8篇 |
1996年 | 8篇 |
1995年 | 6篇 |
1994年 | 1篇 |
1993年 | 3篇 |
1992年 | 2篇 |
1990年 | 5篇 |
1989年 | 2篇 |
1988年 | 3篇 |
1987年 | 1篇 |
1985年 | 7篇 |
1984年 | 2篇 |
1983年 | 3篇 |
1982年 | 4篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 7篇 |
1976年 | 6篇 |
1975年 | 3篇 |
1974年 | 2篇 |
1973年 | 1篇 |
1972年 | 2篇 |
1971年 | 1篇 |
排序方式: 共有272条查询结果,搜索用时 15 毫秒
151.
Gary A. Silverman James C. Whisstock Stephen P. Bottomley James A. Huntington Dion Kaiserman Cliff J. Luke Stephen C. Pak Jean-Marc Reichhart Phillip I. Bird 《The Journal of biological chemistry》2010,285(32):24299-24305
Serpins compose the largest superfamily of peptidase inhibitors and are well known as regulators of hemostasis and thrombolysis. Studies using model organisms, from plants to vertebrates, now show that serpins and their unique inhibitory mechanism and conformational flexibility are exploited to control proteolysis in molecular pathways associated with cell survival, development, and host defense. In addition, an increasing number of non-inhibitory serpins are emerging as important elements within a diversity of biological systems by serving as chaperones, hormone transporters, or anti-angiogenic factors. 相似文献
152.
X-ray crystal structure of MENT: evidence for functional loop-sheet polymers in chromatin condensation
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)
McGowan S Buckle AM Irving JA Ong PC Bashtannyk-Puhalovich TA Kan WT Henderson KN Bulynko YA Popova EY Smith AI Bottomley SP Rossjohn J Grigoryev SA Pike RN Whisstock JC 《The EMBO journal》2006,25(13):3144-3155
Most serpins are associated with protease inhibition, and their ability to form loop-sheet polymers is linked to conformational disease and the human serpinopathies. Here we describe the structural and functional dissection of how a unique serpin, the non-histone architectural protein, MENT (Myeloid and Erythroid Nuclear Termination stage-specific protein), participates in DNA and chromatin condensation. Our data suggest that MENT contains at least two distinct DNA-binding sites, consistent with its simultaneous binding to the two closely juxtaposed linker DNA segments on a nucleosome. Remarkably, our studies suggest that the reactive centre loop, a region of the MENT molecule essential for chromatin bridging in vivo and in vitro, is able to mediate formation of a loop-sheet oligomer. These data provide mechanistic insight into chromatin compaction by a non-histone architectural protein and suggest how the structural plasticity of serpins has adapted to mediate physiological, rather than pathogenic, loop-sheet linkages. 相似文献
153.
Chow MK Amin AA Fulton KF Whisstock JC Buckle AM Bottomley SP 《Protein expression and purification》2006,46(1):166-171
The expression and harvesting of proteins from insoluble inclusion bodies by solubilization and refolding is a technique commonly used in the production of recombinant proteins. To bring clarity to the large and widespread quantity of published protein refolding data, we have recently established the REFOLD database (http://refold.med.monash.edu.au), which is a freely available, open repository for protocols describing the refolding and purification of recombinant proteins. Refolding methods are currently published in many different formats and resources--REFOLD provides a standardized system for the structured reporting and presentation of these data. Furthermore, data in REFOLD are readily accessible using a simple search function, and the database also enables analyses which identify and highlight particular trends between suitable refolding and purification conditions and specific protein properties. This information may in turn serve to facilitate the rational design and development of new refolding protocols for novel proteins. There are approximately 200 proteins currently listed in REFOLD, and it is anticipated that with the continued contribution of data by researchers this number will grow significantly, thus strengthening the emerging trends and patterns and making this database a valuable tool for the scientific community. 相似文献
154.
Peter J.M. Steenbakkers James A. Irving Harry R. Harhangi Willem J.C. Swinkels Anna Akhmanova Rembrandt Dijkerman Mike S.M. Jetten Chris van der Drift James C. Whisstock Huub J.M. Op den Camp 《Mycological Research》2008,112(8):999-1006
A gene encoding a novel component of the cellulolytic complex (cellulosome) of the anaerobic fungus Piromyces sp. strain E2 was identified. The encoded 538 amino acid protein, named celpin, consists of a signal peptide, a positively charged domain of unknown function followed by two fungal dockerins, typical for components of the extracellular fungal cellulosome. The C-terminal end consists of a 380 amino acid serine proteinase inhibitor (or serpin) domain homologue, sharing 30 % identity and 50 % similarity to vertebrate and bacterial serpins. Detailed protein sequence analysis of the serpin domain revealed that it contained all features of a functional serpin. It possesses the conserved amino acids present in more than 70 % of known serpins, and it contained the consensus of inhibiting serpins. Because of the confined space of the fungal cellulosome inside plant tissue and the auto-proteolysis of plant material in the rumen, the fungal serpin is presumably involved in protection of the cellulosome against plant proteinases. The celpin protein of Piromyces sp. strain E2 is the first non-structural, non-hydrolytic fungal cellulosome component. Furthermore, the celpin protein of Piromyces sp. strain E2 is the first representative of a serine proteinase inhibitor of the fungal kingdom. 相似文献
155.
Wong W Wijeyewickrema LC Kennan RM Reeve SB Steer DL Reboul C Smith AI Pike RN Rood JI Whisstock JC Porter CJ 《The Journal of biological chemistry》2011,286(49):42180-42187
The ovine footrot pathogen, Dichelobacter nodosus, secretes three subtilisin-like proteases that play an important role in the pathogenesis of footrot through their ability to mediate tissue destruction. Virulent and benign strains of D. nodosus secrete the basic proteases BprV and BprB, respectively, with the catalytic domain of these enzymes having 96% sequence identity. At present, it is not known how sequence variation between these two putative virulence factors influences their respective biological activity. We have determined the high resolution crystal structures of BprV and BprB. These data reveal that that the S1 pocket of BprV is more hydrophobic but smaller than that of BprB. We show that BprV is more effective than BprB in degrading extracellular matrix components of the host tissue. Mutation of two residues around the S1 pocket of BprB to the equivalent residues in BprV dramatically enhanced its proteolytic activity against elastin substrates. Application of a novel approach for profiling substrate specificity, the Rapid Endopeptidase Profiling Library (REPLi) method, revealed that both enzymes prefer cleaving after hydrophobic residues (and in particular P1 leucine) but that BprV has more restricted primary substrate specificity than BprB. Furthermore, for P1 Leu-containing substrates we found that BprV is a significantly more efficient enzyme than BprB. Collectively, these data illuminate how subtle changes in D. nodosus proteases may significantly influence tissue destruction as part of the ovine footrot pathogenesis process. 相似文献
156.
Laurie L Baker Rodrigo Wiff JC Quiroz Andrés Flores Renato Céspedes Mauricio A. Barrientos Vilma Ojeda Claudio Gatica 《Environmental Biology of Fishes》2014,97(10):1083-1093
The pink cusk-eel (Genypterus blacodes), a benthic-demersal fish confined to the southern hemisphere, supports an important commercial fishery in Chile where it is exploited over an extensive geographic area. Although the fishery was originally divided into a northern (41º28′–47º00′S) and southern (47º00′–57º00′S) zone for the purposes of fisheries management, recent studies have reported significant differences in life history parameters between these zones. Individuals from the southern zone reached larger asymptotic sizes and possessed higher survival rates compared to the northern zone. We estimate and compare the gonadosomatic index (GSI), shape of the maturity ogive, and length at 50 % maturity (L 50%) of female G. blacodes between management zones and across time using biological data collected from the industrial fleet between 1985 and 2009. Females in the northern zone had higher monthly mean GSI than females in the southern zone. Our analyses also revealed L 50% to be significantly higher in the southern zone than in the northern zone from 1985 to 2009. The significant differences in life-history traits between fishery management zones agree with the trade-offs predicted by Charnov’s life history theory. Together these results provide additional support for the hypothesis that two separate stocks exist and suggest that females from the northern zone have developed a life-history strategy, which favours early maturation and a proportionally greater investment in reproduction than females from the southern zone. 相似文献
157.
Frédéric D Chevalier Claudia LL Valentim Philip T LoVerde Timothy JC Anderson 《BMC genomics》2014,15(1)
Background
Identification of parasite genes that underlie traits such as drug resistance and host specificity is challenging using classical linkage mapping approaches. Extreme QTL (X-QTL) methods, originally developed by rodent malaria and yeast researchers, promise to increase the power and simplify logistics of linkage mapping in experimental crosses of schistosomes (or other helminth parasites), because many 1000s of progeny can be analysed, phenotyping is not required, and progeny pools rather than individuals are genotyped. We explored the utility of this method for mapping a drug resistance gene in the human parasitic fluke Schistosoma mansoni.Results
We staged a genetic cross between oxamniquine sensitive and resistant parasites, then between two F1 progeny, to generate multiple F2 progeny. One group of F2s infecting hamsters was treated with oxamniquine, while a second group was left untreated. We used exome capture to reduce the size of the genome (from 363 Mb to 15 Mb) and exomes from pooled F2 progeny (treated males, untreated males, treated females, untreated females) and the two parent parasites were sequenced to high read depth (mean = 95-366×) and allele frequencies at 14,489 variants compared. We observed dramatic enrichment of alleles from the resistant parent in a small region of chromosome 6 in drug-treated male and female pools (combined analysis: = 11.07, p = 8.74 × 10-29). This region contains Smp_089320 a gene encoding a sulfotransferase recently implicated in oxamniquine resistance using classical linkage mapping methods.Conclusions
These results (a) demonstrate the utility of exome capture for generating reduced representation libraries in Schistosoma mansoni, and (b) provide proof-of-principle that X-QTL methods can be successfully applied to an important human helminth. The combination of these methods will simplify linkage analysis of biomedically or biologically important traits in this parasite.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-617) contains supplementary material, which is available to authorized users. 相似文献158.
Rapid screening for phenotype-genotype associations by linear transformations of genomic evaluations
Jose L Gualdrón Duarte Rodolfo JC Cantet Ronald O Bates Catherine W Ernst Nancy E Raney Juan P Steibel 《BMC bioinformatics》2014,15(1)
Background
Currently, association studies are analysed using statistical mixed models, with marker effects estimated by a linear transformation of genomic breeding values. The variances of marker effects are needed when performing the tests of association. However, approaches used to estimate the parameters rely on a prior variance or on a constant estimate of the additive variance. Alternatively, we propose a standardized test of association using the variance of each marker effect, which generally differ among each other. Random breeding values from a mixed model including fixed effects and a genomic covariance matrix are linearly transformed to estimate the marker effects.Results
The standardized test was neither conservative nor liberal with respect to type I error rate (false-positives), compared to a similar test using Predictor Error Variance, a method that was too conservative. Furthermore, genomic predictions are solved efficiently by the procedure, and the p-values are virtually identical to those calculated from tests for one marker effect at a time. Moreover, the standardized test reduces computing time and memory requirements.The following steps are used to locate genome segments displaying strong association. The marker with the highest − log(p-value) in each chromosome is selected, and the segment is expanded one Mb upstream and one Mb downstream of the marker. A genomic matrix is calculated using the information from those markers only, which is used as the variance-covariance of the segment effects in a model that also includes fixed effects and random genomic breeding values. The likelihood ratio is then calculated to test for the effect in every chromosome against a reduced model with fixed effects and genomic breeding values. In a case study with pigs, a significant segment from chromosome 6 explained 11% of total genetic variance.Conclusions
The standardized test of marker effects using their own variance helps in detecting specific genomic regions involved in the additive variance, and in reducing false positives. Moreover, genome scanning of candidate segments can be used in meta-analyses of genome-wide association studies, as it enables the detection of specific genome regions that affect an economically relevant trait when using multiple populations.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2105-15-246) contains supplementary material, which is available to authorized users. 相似文献159.
Background
The complex societies of ants and other social insects rely on sophisticated chemical communication. Two families of small soluble proteins, the odorant binding and chemosensory proteins (OBPs and CSPs), are believed to be important in insect chemosensation. To better understand the role of these proteins in ant olfaction, we examined their evolution and expression across the ants using phylogenetics and sex- and tissue-specific RNA-seq.Results
We find that subsets of both OBPs and CSPs are expressed in the antennae, contradicting the previous hypothesis that CSPs have replaced OBPs in ant olfaction. Both protein families have several highly conserved clades with a single ortholog in all eusocial hymenopterans, as well as clades with more dynamic evolution and many taxon-specific radiations. The dynamically evolving OBPs and CSPs have been hypothesized to function in chemical communication. Intriguingly, we find that seven members of the conserved clades are expressed specifically in the antennae of the clonal raider ant Cerapachys biroi, whereas only one dynamically evolving CSP is antenna specific. The orthologs of the conserved, antenna-specific C. biroi genes are also expressed in antennae of the ants Camponotus floridanus and Harpegnathos saltator, indicating that antenna-specific expression of these OBPs and CSPs is conserved across ants. Most members of the dynamically evolving clades in both protein families are expressed primarily in non-chemosensory tissues and thus likely do not fulfill chemosensory functions.Conclusions
Our results identify candidate OBPs and CSPs that are likely involved in conserved aspects of ant olfaction, and suggest that OBPs and CSPs may not rapidly evolve to recognize species-specific signals.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-718) contains supplementary material, which is available to authorized users. 相似文献160.
Norbert Meyer Jan W Dallinga Sarah Janine Nuss Edwin JC Moonen Joep JBN van Berkel Cezmi Akdis Frederik Jan van Schooten Günter Menz 《Respiratory research》2014,15(1)