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51.
B C Broughton A R Lehmann S A Harcourt C F Arlett A Sarasin W J Kleijer F A Beemer R Nairn D L Mitchell 《Mutation research》1990,235(1):33-40
Trichothiodystrophy is a genetic disease which in the majority of cases studied is associated with a deficiency in the ability to repair UV damage in cellular DNA. Three categories of UV response have been identified. In type 1 the response is completely normal, whereas type 2 cells are deficient in excision-repair, with properties indistinguishable from those of XP complementation group D. Type 3 cells have normal survival following UV-irradiation and normal rates of removal of cyclobutane pyrimidine dimer sites. Nevertheless repair synthesis is reduced by 50% in these cell strains and this is associated with a marked reduction in the repair of 6-4 photoproducts from cellular DNA. The present results show that 50% or more of repair synthesis at early times after irradiation of normal primary human fibroblasts is attributable to repair of 6-4 products. They also suggest that repair of cyclobutane dimers is crucial for cell survival. 相似文献
52.
Distribution and characterization of a Sandhoff disease-associated 50-kb deletion in the gene encoding the human β-hexosaminidase β-chain 总被引:1,自引:1,他引:0
Hennie Bikker Frank M. van den Berg Ruud A. Wolterman Wim J. Kleijer Jan J. M. de Vijlder Piet A. Bolhuis 《Human genetics》1990,85(3):327-329
Summary A 50-kb deletion was demonstrated in the gene encoding for the -subunit of human hexosaminidase (HEXB), using field inversion gel electrophoresis (FIGE) of SfiI-digested chromosomal DNA from patients with Sandhoff disease. We investigated 14 patients from different parts of Europe and found no deletion in 5 patients, 2 patients homozygous for the deletion, and 7 patients with the deletion in one allele. The distribution of the 50-kb deletion was approximately in agreement with the Hardy-Weinberg equilibrium. The deletion was characterized using chromosomal DNA from one of the two homozygous patients. Restriction fragments were hybridized with a 1.6-kb (almost complete) and a 0.4-kb (5) HEXB cDNA clone. It appeared that the deletion started in intron 5, extending in the 5 direction and causing the loss of exon 1–5 and the promoter area of the HEXB gene. 相似文献
53.
The Olifants River, a tributary of the Limpopo River system, is one of the most polluted rivers in South Africa. In May 2011 the concentrations of metals in fish muscle tissue from two impoundments, Loskop and Flag Boshielo dams, on the Olifants River were measured and a human health risk assessment conducted to investigate whether it was safe to consume Labeo rosae from these impoundments. Labeo rosae is one of the most common pan fish in these impoundments and is readily available to rural communities. Metals are accumulating in the muscle tissue of L. rosae even although the fish populations appear to be healthy. At Loskop Dam all L. rosae analysed exceeded the recommended hazard quotient (HQ) of 1 for antimony, and less than 50% exceeded that for lead. At Flag Boshielo Dam, the recommended HQ was exceeded for lead in less than 50% of L. rosae analysed, and more than 50% exceeded that for antimony. The weekly consumption of 150?g of L. rosae muscle tissue from these impoundments may pose an unacceptable health risk to rural communities. 相似文献
54.
Repair replication in heterokaryons deprived from different repair-deficient xeroderma pigmentosum strains 总被引:3,自引:0,他引:3
Repair replication was studied in UV-irradiated cell populations obtained after fusion of cell strains originating from different xeroderma pigmentosum (XP) patients. The capacity to perform repair replication appeared to be restored completely in multinucleate heterokaryons resulting from fusion between a classic XP-strain and a De Sanctis-Cacchione (DSC) strain. In cell populations obtained by fusion of either two different classic XP strains or two different DSC strains no repair replication was observed.These results, obtained with the technique of density labelling and isopycnic centrifugation of DNA, confirm our previously reported results of autoradiographic studies of unscheduled DNA synthesis. The occurrence of complementation between a classic XP strain and a DSC strain indicates that the defect in the two forms of the disease is caused by different mutations. 相似文献
55.
M L Bermingham S C Bishop J A Woolliams R Pong-Wong A R Allen S H McBride J J Ryder D M Wright R A Skuce S WJ McDowell E J Glass 《Heredity》2014,112(5):543-551
Tuberculosis (TB) caused by Mycobacterium bovis is a re-emerging disease of
livestock that is of major economic importance worldwide, as well as being a zoonotic
risk. There is significant heritability for host resistance to bovine TB (bTB) in dairy
cattle. To identify resistance loci for bTB, we undertook a genome-wide association study
in female Holstein–Friesian cattle with 592 cases and 559 age-matched controls from
case herds. Cases and controls were categorised into distinct phenotypes: skin test and
lesion positive vs skin test negative on multiple occasions, respectively. These animals
were genotyped with the Illumina BovineHD 700K BeadChip. Genome-wide rapid association
using linear and logistic mixed models and regression (GRAMMAR), regional heritability
mapping (RHM) and haplotype-sharing analysis identified two novel resistance loci that
attained chromosome-wise significance, protein tyrosine phosphatase receptor T
(PTPRT; P=4.8 × 10−7) and myosin
IIIB (MYO3B; P=5.4 × 10−6). We estimated
that 21% of the phenotypic variance in TB resistance could be explained by all of
the informative single-nucleotide polymorphisms, of which the region encompassing the
PTPRT gene accounted for 6.2% of the variance and a further 3.6%
was associated with a putative copy number variant in MYO3B. The results from
this study add to our understanding of variation in host control of infection and suggest
that genetic marker-based selection for resistance to bTB has the potential to make a
significant contribution to bTB control. 相似文献
56.
Edward WJ Curry 《BMC bioinformatics》2014,15(1)
Background
A generalized notion of biclustering involves the identification of patterns across subspaces within a data matrix. This approach is particularly well-suited to analysis of heterogeneous molecular biology datasets, such as those collected from populations of cancer patients. Different definitions of biclusters will offer different opportunities to discover information from datasets, making it pertinent to tailor the desired patterns to the intended application. This paper introduces ‘GABi’, a customizable framework for subspace pattern mining suited to large heterogeneous datasets. Most existing biclustering algorithms discover biclusters of only a few distinct structures. However, by enabling definition of arbitrary bicluster models, the GABi framework enables the application of biclustering to tasks for which no existing algorithm could be used.Results
First, a series of artificial datasets were constructed to represent three clearly distinct scenarios for applying biclustering. With a bicluster model created for each distinct scenario, GABi is shown to recover the correct solutions more effectively than a panel of alternative approaches, where the bicluster model may not reflect the structure of the desired solution. Secondly, the GABi framework is used to integrate clinical outcome data with an ovarian cancer DNA methylation dataset, leading to the discovery that widespread dysregulation of DNA methylation associates with poor patient prognosis, a result that has not previously been reported. This illustrates a further benefit of the flexible bicluster definition of GABi, which is that it enables incorporation of multiple sources of data, with each data source treated in a specific manner, leading to a means of intelligent integrated subspace pattern mining across multiple datasets.Conclusions
The GABi framework enables discovery of biologically relevant patterns of any specified structure from large collections of genomic data. An R implementation of the GABi framework is available through CRAN (http://cran.r-project.org/web/packages/GABi/index.html).Electronic supplementary material
The online version of this article (doi:10.1186/s12859-014-0355-5) contains supplementary material, which is available to authorized users. 相似文献57.
Mohamed M Thabet Thomas WJ Huizinga Désirée M van der Heijde Annette HM van der Helm-van Mil 《Arthritis research & therapy》2009,11(5):1-9
Introduction
Evidence suggests that citrullinated fibrin(ogen) may be a potential in vivo target of anticitrullinated protein/peptide antibodies (ACPA) in rheumatoid arthritis (RA). We compared the diagnostic yield of three enzyme-linked immunosorbent assay (ELISA) tests by using chimeric fibrin/filaggrin citrullinated synthetic peptides (CFFCP1, CFFCP2, CFFCP3) with a commercial CCP2-based test in RA and analyzed their prognostic values in early RA.Methods
Samples from 307 blood donors and patients with RA (322), psoriatic arthritis (133), systemic lupus erythematosus (119), and hepatitis C infection (84) were assayed by using CFFCP- and CCP2-based tests. Autoantibodies also were analyzed at baseline and during a 2-year follow-up in 98 early RA patients to determine their prognostic value.Results
With cutoffs giving 98% specificity for RA versus blood donors, the sensitivity was 72.1% for CFFCP1, 78.0% for CFFCP2, 71.4% for CFFCP3, and 73.9% for CCP2, with positive predictive values greater than 97% in all cases. CFFCP sensitivity in RA increased to 80.4% without losing specificity when positivity was considered as any positive anti-CFFCP status. Specificity of the three CFFCP tests versus other rheumatic populations was high (> 90%) and similar to those for the CCP2. In early RA, CFFCP1 best identified patients with a poor radiographic outcome. Radiographic progression was faster in the small subgroup of CCP2-negative and CFFCP1-positive patients than in those negative for both autoantibodies. CFFCP antibodies decreased after 1 year, but without any correlation with changes in disease activity.Conclusions
CFFCP-based assays are highly sensitive and specific for RA. Early RA patients with anti-CFFCP1 antibodies, including CCP2-negative patients, show greater radiographic progression. 相似文献58.
Global concerns about climate changes and their association with the use of fossil fuels have accelerated research on biological
fuel production. Biological hydrogen production from hemicellulose-containing waste is considered one of the promising avenues.
A major economical issue for such a process, however, is the low substrate conversion efficiency. Interestingly, the extreme
thermophilic bacterium Caldicellulosiruptor saccharolyticus can produce hydrogen from carbohydrate-rich substrates at yields close to the theoretical maximum of the dark fermentation
process (i.e., 4 mol H2/mol hexose). The organism is able to ferment an array of mono-, di- and polysaccharides, and is relatively tolerant to high
partial hydrogen pressures, making it a promising candidate for exploitation in a biohydrogen process. The behaviour of this
Gram-positive bacterium bears all hallmarks of being adapted to an environment sparse in free sugars, which is further reflected
in its low volumetric hydrogen productivity and low osmotolerance. These two properties need to be improved by at least a
factor of 10 and 5, respectively, for a cost-effective industrial process. In this review, the physiological characteristics
of C. saccharolyticus are analyzed in view of the requirements for an efficient hydrogen cell factory. A special emphasis is put on the tight regulation
of hydrogen production in C. saccharolyticus by both redox and energy metabolism. Suggestions for strategies to overcome the current challenges facing the potential use
of the organism in hydrogen production are also discussed. 相似文献
59.
Background
The three consensus elements at the 3' end of human introns - the branch point sequence, the polypyrimidine tract, and the 3' splice site AG dinucleotide - are usually closely spaced within the final 40 nucleotides of the intron. However, the branch point sequence and polypyrimidine tract of a few known alternatively spliced exons lie up to 400 nucleotides upstream of the 3' splice site. The extended regions between the distant branch points (dBPs) and their 3' splice site are marked by the absence of other AG dinucleotides. In many cases alternative splicing regulatory elements are located within this region.Results
We have applied a simple algorithm, based on AG dinucleotide exclusion zones (AGEZ), to a large data set of verified human exons. We found a substantial number of exons with large AGEZs, which represent candidate dBP exons. We verified the importance of the predicted dBPs for splicing of some of these exons. This group of exons exhibits a higher than average prevalence of observed alternative splicing, and many of the exons are in genes with some human disease association.Conclusion
The group of identified probable dBP exons are interesting first because they are likely to be alternatively spliced. Second, they are expected to be vulnerable to mutations within the entire extended AGEZ. Disruption of splicing of such exons, for example by mutations that lead to insertion of a new AG dinucleotide between the dBP and 3' splice site, could be readily understood even though the causative mutation might be remote from the conventional locations of splice site sequences. 相似文献60.
Kim D Baas Maarten WJ Koeter Henk C van Weert Peter Lucassen Claudi LH Bockting Karin A Wittkampf Aart H Schene 《Trials》2010,11(1):1-6