全文获取类型
收费全文 | 88篇 |
免费 | 5篇 |
专业分类
93篇 |
出版年
2018年 | 1篇 |
2017年 | 1篇 |
2016年 | 2篇 |
2015年 | 5篇 |
2014年 | 9篇 |
2013年 | 5篇 |
2012年 | 5篇 |
2011年 | 3篇 |
2010年 | 6篇 |
2009年 | 1篇 |
2008年 | 3篇 |
2007年 | 1篇 |
2006年 | 3篇 |
2005年 | 2篇 |
2003年 | 1篇 |
2002年 | 1篇 |
1999年 | 3篇 |
1998年 | 6篇 |
1997年 | 3篇 |
1996年 | 3篇 |
1993年 | 2篇 |
1992年 | 2篇 |
1990年 | 4篇 |
1989年 | 5篇 |
1988年 | 3篇 |
1987年 | 2篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1980年 | 2篇 |
1978年 | 1篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1968年 | 1篇 |
1912年 | 1篇 |
排序方式: 共有93条查询结果,搜索用时 0 毫秒
41.
Y Deng J Zhao D Sakurai KM Kaufman JC Edberg RP Kimberly DL Kamen GS Gilkeson CO Jacob RH Scofield CD Langefeld JA Kelly ME Alarcón-Riquelme BIOLUPUS GENLES Networks JB Harley TJ Vyse BI Freedman PM Gaffney KM Sivils JA James TB Niewold RM Cantor W Chen BH Hahn EE Brown PROFILE BP Tsao 《Arthritis research & therapy》2012,14(Z3):A5
42.
Budding yeast Rif1 binds to replication origins and protects DNA at blocked replication forks 下载免费PDF全文
Shin‐ichiro Hiraga Chandre Monerawela Yuki Katou Sophie Shaw Kate RM Clark Katsuhiko Shirahige Anne D Donaldson 《EMBO reports》2018,19(9)
Despite its evolutionarily conserved function in controlling DNA replication, the chromosomal binding sites of the budding yeast Rif1 protein are not well understood. Here, we analyse genome‐wide binding of budding yeast Rif1 by chromatin immunoprecipitation, during G1 phase and in S phase with replication progressing normally or blocked by hydroxyurea. Rif1 associates strongly with telomeres through interaction with Rap1. By comparing genomic binding of wild‐type Rif1 and truncated Rif1 lacking the Rap1‐interaction domain, we identify hundreds of Rap1‐dependent and Rap1‐independent chromosome interaction sites. Rif1 binds to centromeres, highly transcribed genes and replication origins in a Rap1‐independent manner, associating with both early and late‐initiating origins. Interestingly, Rif1 also binds around activated origins when replication progression is blocked by hydroxyurea, suggesting association with blocked forks. Using nascent DNA labelling and DNA combing techniques, we find that in cells treated with hydroxyurea, yeast Rif1 stabilises recently synthesised DNA. Our results indicate that, in addition to controlling DNA replication initiation, budding yeast Rif1 plays an ongoing role after initiation and controls events at blocked replication forks. 相似文献
43.
Tanya Marchant Ritgak Dimka Tilley-Gyado Tsegahun Tessema Kultar Singh Meenakshi Gautham Nasir Umar Della Berhanu Simon Cousens Joanna RM Armstrong Schellenberg 《PloS one》2015,10(5)
BackgroundFamilies in high mortality settings need regular contact with high quality services, but existing population-based measurements of contacts do not reflect quality. To address this, in 2012, we designed linked household and frontline worker surveys for Gombe State, Nigeria, Ethiopia, and Uttar Pradesh, India. Using reported frequency and content of contacts, we present a method for estimating the population level coverage of high quality contacts.ConclusionsMeasuring content of care to reflect the quality of contacts can reveal missed opportunities to deliver best possible health care. 相似文献
44.
Bradley RD; Adkins RM; Honeycutt RL; McDonald JH 《Molecular biology and evolution》1998,15(6):709-717
Using the strictly neutral model as a null hypothesis, we tested for
deviations from expected levels of nucleotide polymorphism at the alcohol
dehydrogenase locus (Adh-1) within and among four species of pocket gophers
(Geomys bursarius major, G. knoxjonesi, G. texensis llanensis, and G.
attwateri). The complete protein-encoding region was examined, and 10
unique alleles, representing both electromorphic and cryptic alleles, were
used to test hypotheses (e.g., the neutral model) concerning the
maintenance of genetic variation. Nineteen variable sites were identified
among the 10 alleles examined, including 9 segregating sites occurring in
synonymous positions and 10 that were nonsynonymous. Several statistical
methods, including those that test for within-species variation as well as
those that examine variation within and among species, failed to reject the
null hypothesis that variation (both within and between species of Geomys)
at the Adh locus is consistent with the neutral theory. However, there was
significant heterogeneity in the ratio of polymorphism to divergence across
the gene, with polymorphisms clustered in the first half of the coding
region and fixed differences clustered in the second half of the gene. Two
alternative hypotheses are discussed as possible explanations for this
heterogeneity: an old balanced polymorphism in the first half of the gene
or a recent selective sweep in the second half of the gene.
相似文献
45.
Robson Sartorello Alexandre Budu Piero Bagnaresi Carlos AH Fernandes Paloma M. Sato Vânia B. Bueno Marcos RM Fontes Pedro L. Oliveira Gabriela O. Paiva‐Silva Simone V. Alves Luis ES Netto Luiz H. Catalani Celia RS Garcia 《Cell biology international》2010,34(8):859-865
The cellular traffic of haem during the development of the human malaria parasite Plasmodium falciparum, through the stages R (ring), T (trophozoite) and S (schizonts), was investigated within RBC (red blood cells). When Plasmodium cultures were incubated with a fluorescent haem analogue, ZnPPIX (Zn protoporphyrin IX) the probe was seen at the cytoplasm (R stage), and the vesicle‐like structure distribution pattern was more evident at T and S stages. The temporal sequence of ZnPPIX uptake byP. falciparum‐infected erythrocytes shows that at R and S stages, a time‐increase acquisition of the porphyrin reaches the maximum fluorescence distribution after 60 min; in contrast, at the T stage, the maximum occurs after 120 min of ZnPPIX uptake. The difference in time‐increase acquisition of the porphyrin is in agreement with a maximum activity of haem uptake at the T stage. To gain insights into haem metabolism, recombinant PfHO (P. falciparum haem oxygenase) was expressed, and the conversion of haem into BV (biliverdin) was detected. These findings point out that, in addition to haemozoin formation, the malaria parasite P. falciparum has evolved two distinct mechanisms for dealing with haem toxicity, namely, the uptake of haem into a cellular compartment where haemozoin is formed and HO activity. However, the low Plasmodium HO activity detected reveals that the enzyme appears to be a very inefficient way to scavenge the haem compared with the Plasmodium ability to uptake the haem analogue ZnPPIX and delivering it to the food vacuole. 相似文献
46.
Reduced natural selection associated with low recombination in Drosophila melanogaster 总被引:8,自引:1,他引:7
Synonymous codons are not used equally in many organisms, and the extent of
codon bias varies among loci. Earlier studies have suggested that more
highly expressed loci in Drosophila melanogaster are more biased,
consistent with findings from several prokaryotes and unicellular
eukaryotes that codon bias is partly due to natural selection for
translational efficiency. We link this model of varying selection intensity
to the population-genetics prediction that the effectiveness of natural
selection is decreased under reduced recombination. In analyses of 385 D.
melanogaster loci, we find that codon bias is reduced in regions of low
recombination (i.e., near centromeres and telomeres and on the fourth
chromosome). The effect does not appear to be a linear function of
recombination rate; rather, it seems limited to regions with the very
lowest levels of recombination. The large majority of the genome apparently
experiences recombination at a sufficiently high rate for effective natural
selection against suboptimal codons. These findings support models of the
Hill-Robertson effect and genetic hitchhiking and are largely consistent
with multiple reports of low levels of DNA sequence variation in regions of
low recombination.
相似文献
47.
Kappa-chain constant-region gene sequences in genus Rattus: coding regions are diverging more rapidly than noncoding regions 总被引:2,自引:0,他引:2
We have determined the nucleotide sequence of a 1,200-base pair (bp)
genomic fragment that includes the kappa-chain constant-region gene (C
kappa) from two species of native Australian rodents, Rattus leucopus
cooktownensis and Rattus colletti. Comparison of these sequences with each
other and with other rodent C kappa genes shows three surprising features.
First, the coding regions are diverging at a rate severalfold higher than
that of the nearby noncoding regions. Second, replacement changes within
the coding region are accumulating at a rate at least as great as that of
silent changes. Third, most of the amino acid replacements are localized in
one region of the C kappa domain--namely, the carboxy-terminal "bends" in
the alpha-carbon backbone. These three features have previously been
described from comparisons of the two allelic forms of C kappa genes in R.
norvegicus. These data imply the existence of considerable evolutionary
constraints on the noncoding regions (based on as yet undetermined
functions) or powerful positive selection to diversify a portion of the
constant-region domain (whose physiological significance is not known).
These surprising features of C kappa evolution appear to be characteristic
only of closely related C kappa genes, since comparison of rodent with
human sequences shows the expected greater conservation of coding regions,
as well as a predominance of silent nucleotide substitutions within the
coding regions.
相似文献
48.
Becca Asquith Angelina J Mosley Adrian Heaps Yuetsu Tanaka Graham P Taylor Angela R McLean Charles RM Bangham 《Retrovirology》2005,2(1):1-9
Background
Cellular infection with human immunodeficiency virus (HIV) both in vitro and in vivo requires a member of the chemokine receptor family to act as a co-receptor for viral entry. However, it is presently unclear to what extent the interaction of HIV proteins with chemokine receptors generates intracellular signals that are important for productive infection.Results
In this study we have used a recently described family of chemokine inhibitors, termed BSCIs, which specifically block chemokine-induced chemotaxis without affecting chemokine ligands binding to their receptors. The BSCI termed Peptide 3 strongly inhibited CCR5 mediated HIV infection of THP-1 cells (83 ± 7% inhibition assayed by immunofluoresence staining), but had no effect on gp120 binding to CCR5. Peptide 3 did not affect CXCR4-dependent infection of Jurkat T cells.Conclusion
These observations suggest that, in some cases, intracellular signals generated by the chemokine coreceptor may be required for a productive HIV infection. 相似文献49.
Clonal rat parathyroid cell line expresses a parathyroid hormone-related peptide but not parathyroid hormone itself 总被引:3,自引:0,他引:3
K Ikeda E C Weir K Sakaguchi W J Burtis M Zimering M Mangin B E Dreyer M L Brandi G D Aurbach A E Broadus 《Biochemical and biophysical research communications》1989,162(1):108-115
A novel parathyroid hormone-related peptide has been identified in tumors associated with the syndrome of humoral hypercalcemia of malignancy. Subsequently, mRNAs encoding this peptide have been found to be expressed in a number of normal tissues, including the parathyroids. Using Northern blotting, RNase protection, and immunochemical techniques, we examined a clonal rat parathyroid cell line originally developed as a model system for studying parathyroid cell physiology. We found that this line expresses the parathyroid hormone-related peptide but not parathyroid hormone itself. Secretion of the parathyroid hormone-related peptide varied inversely with extracellular calcium concentration, but neither calcium nor 1,25-dihydroxyvitamin D3 appeared to influence steady-state parathyroid hormone-related peptide mRNA levels. This clonal line may prove to be an interesting system for studying the factors responsible for tissue-specific parathyroid hormone and parathyroid hormone-related peptide gene expression. 相似文献
50.
Abstract Marine polymetallic sulfides (MPS) are recently discovered mineral occurrences of hydrothermal origin. Design of an appropriate research strategy to investigate the MPS deposits is a policy issue that the paper seeks to help resolve. The paper describes the relevant nature of MPS, reviews what has happened in the early stages of MPS research, and examines market conditions to help specify a scientifically and economically effective research strategy. This strategy is examined in several key dimensions: science versus research and development (R&D); role of government and private industry, geographic concentration; focus in time; and the locus of responsibility and scope of participation. Because of the early stage of work on MPS and the scant scientific evidence available, expected results of R&D are extremely uncertain. In this context, a sequential scientific approach is favored for government support. The strategy suggested by the paper's analysis would permit geographically varied work sites and would incorporate diversification of research approaches, decentralization of discretionary decision‐making, and a broad base of participation. 相似文献