全文获取类型
收费全文 | 80篇 |
免费 | 4篇 |
出版年
2021年 | 1篇 |
2020年 | 2篇 |
2017年 | 1篇 |
2016年 | 2篇 |
2015年 | 2篇 |
2014年 | 5篇 |
2013年 | 3篇 |
2012年 | 2篇 |
2011年 | 6篇 |
2010年 | 5篇 |
2009年 | 4篇 |
2008年 | 2篇 |
2007年 | 4篇 |
2006年 | 1篇 |
2005年 | 1篇 |
2004年 | 2篇 |
2003年 | 1篇 |
1998年 | 5篇 |
1997年 | 2篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1994年 | 3篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 5篇 |
1988年 | 3篇 |
1987年 | 3篇 |
1986年 | 3篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 3篇 |
1979年 | 1篇 |
1977年 | 1篇 |
1964年 | 1篇 |
1962年 | 1篇 |
1961年 | 1篇 |
排序方式: 共有84条查询结果,搜索用时 15 毫秒
41.
Raffael AC Oliveira Ricardo VM Almeida Márcia DA Dantas Felipe N Castro Jo?o Paulo MS Lima Daniel CF Lanza 《BMC bioinformatics》2014,15(1)
Background
The PCR technique and its variations have been increasingly used in the clinical laboratory and recent advances in this field generated new higher resolution techniques based on nucleic acid denaturation dynamics. The principle of these new molecular tools is based on the comparison of melting profiles, after denaturation of a DNA double strand. Until now, the secondary structure of single-stranded nucleic acids has not been exploited to develop identification systems based on PCR. To test the potential of single-strand RNA denaturation as a new alternative to detect specific nucleic acid variations, sequences from viruses of the Totiviridae family were compared using a new in silico melting curve approach. This family comprises double-stranded RNA virus, with a genome constituted by two ORFs, ORF1 and ORF2, which encodes the capsid/RNA binding proteins and an RNA-dependent RNA polymerase (RdRp), respectively.Results
A phylogenetic tree based on RdRp amino acid sequences was constructed, and eight monophyletic groups were defined. Alignments of RdRp RNA sequences from each group were screened to identify RNA regions with conserved secondary structure. One region in the second half of ORF2 was identified and individually modeled using the RNAfold tool. Afterwards, each DNA or RNA sequence was denatured in silico using the softwares MELTSIM and RNAheat that generate melting curves considering the denaturation of a double stranded DNA and single stranded RNA, respectively. The same groups identified in the RdRp phylogenetic tree were retrieved by a clustering analysis of the melting curves data obtained from RNAheat. Moreover, the same approach was used to successfully discriminate different variants of Trichomonas vaginalis virus, which was not possible by the visual comparison of the double stranded melting curves generated by MELTSIM.Conclusion
In silico analysis indicate that ssRNA melting curves are more informative than dsDNA melting curves. Furthermore, conserved RNA structures may be determined from analysis of individuals that are phylogenetically related, and these regions may be used to support the reconstitution of their phylogenetic groups. These findings are a robust basis for the development of in vitro systems to ssRNA melting curves detection.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2105-15-243) contains supplementary material, which is available to authorized users. 相似文献42.
Ying J Nie Mo Y Mok Godfrey CF Chan Albert W Chan Ou Jin Sushma Kavikondala Albert KW Lie Chak S Lau 《Arthritis research & therapy》2010,12(3):R91
Introduction
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoreactive T and B cells, which are believed to be secondary to deficient dendritic cells (DCs). However, whether DC abnormalities occur during their development in the bone marrow (BM) or in the periphery is not known. 相似文献43.
Lee SF Srinivasan B Sephton CF Dries DR Wang B Yu C Wang Y Dewey CM Shah S Jiang J Yu G 《The Journal of biological chemistry》2011,286(31):27447-27453
Notch is a transmembrane receptor that controls a diverse array of cellular processes including cell proliferation, differentiation, survival, and migration. The cellular outcome of Notch signaling is dependent on extracellular and intracellular signals, but the complexities of its regulation are not well understood. Canonical Notch signaling involves ligand association that triggers sequential and regulated proteolysis of Notch at several sites. Ligand-dependent proteolysis at the S2 site removes the bulk of the extracellular domain of Notch. Subsequent γ-secretase-mediated intramembrane proteolysis of the remaining membrane-tethered Notch fragment at the S3 site produces a nuclear-destined Notch intracellular domain (NICD). Here we show that following γ-secretase cleavage, Notch is proteolyzed at a novel S5 site. We have identified this S5 site to be eight amino acids downstream of the S3 site. Biochemical fractionation and purification resulted in the identification of the S5 site protease as the mitochondrial intermediate peptidase (MIPEP). Expression of the MIPEP-cleaved NICD (ΔNICD) results in a decrease in cell viability and mitochondria membrane potential. The sequential and regulated proteolysis by γ-secretase and MIPEP suggests a new means by which Notch function can be modulated. 相似文献
44.
Mattia CF Prosperi Luciano Prosperi Alessandro Bruselles Isabella Abbate Gabriella Rozera Donatella Vincenti Maria Carmela Solmone Maria Rosaria Capobianchi Giovanni Ulivi 《BMC bioinformatics》2011,12(1):5
Background
Next-generation sequencing (NGS) offers a unique opportunity for high-throughput genomics and has potential to replace Sanger sequencing in many fields, including de-novo sequencing, re-sequencing, meta-genomics, and characterisation of infectious pathogens, such as viral quasispecies. Although methodologies and software for whole genome assembly and genome variation analysis have been developed and refined for NGS data, reconstructing a viral quasispecies using NGS data remains a challenge. This application would be useful for analysing intra-host evolutionary pathways in relation to immune responses and antiretroviral therapy exposures. Here we introduce a set of formulae for the combinatorial analysis of a quasispecies, given a NGS re-sequencing experiment and an algorithm for quasispecies reconstruction. We require that sequenced fragments are aligned against a reference genome, and that the reference genome is partitioned into a set of sliding windows (amplicons). The reconstruction algorithm is based on combinations of multinomial distributions and is designed to minimise the reconstruction of false variants, called in-silico recombinants. 相似文献45.
Substantial mortalities of Atlantic salmon (Salmo salar) at two aquaculture sites in Long Island Sound, off Grand Manan Island, Bay of Fundy (BoF) (New Brunswick, Canada) in September 2003, were associated with a bloom of Alexandrium fundyense (>3 × 105 cells L−1), a dinoflagellate alga that produces toxins which cause paralytic shellfish poisoning (PSP). Cells of A. fundyense collected from surface waters while fish were dying had total paralytic shellfish (PS) toxin concentrations of 70.6 pg STX equiv. (saxitoxin equivalents) cell−1 and PS toxin profiles rich in carbamate toxins (78.2%). The zooplankton sampled contained PS toxins (63.1 pg STX equiv. g−1 wet wt) and the toxin profile matched that of A. fundyense cells.Mean PS toxin levels were low (<4 μg STX equiv. 100 g−1 wet wt) in stomach, gill and muscle tissues of moribund salmon, suggesting that PS toxins are very lethal to salmon.The PS toxin concentrations in blue mussels (Mytilus edulis) growing on the salmon cages (37; 526 μg STX equiv. 100 g−1 wet wt) were the highest recorded to date from this region. Their PS toxin profiles showed enhanced carbamate contents (85.5%) compared with that found in A. fundyense. Blue mussels collected from an adjacent Canadian Food Inspection Agency (CFIA) monitoring site in Grand Manan had PS toxin concentrations of 4214 and 150 μg STX equiv. 100 g−1 wet wt in late September and December, respectively, well above the regulatory limit (RL), and horse mussels (Modiolus modiolus) collected in late September had PS toxin concentrations of 2357 μg STX equiv. 100 g−1 wet wt. Detoxification under laboratory conditions suggested that blue mussels may require up to 19 weeks for elimination below RL when they accumulate these high concentrations of PS toxins. This depuration period may be shorter in the field.PS toxin levels above RL were detected in hepatopancreatic tissues of lobster (Homarus americanus), with lower levels (<16 μg STX equiv. 100 g−1 wet wt) in tail muscle and gills.These results illustrate the movement of PS toxins through the marine food chain following an A. fundyense bloom in the BoF, and support earlier studies suggesting that kills from the region of zooplanktivorous fish, such as herring (Clupea harengus harengus), can be attributed to blooms of A. fundyense. This is the first reported incident of PSP associated with mortalities of caged Atlantic salmon in the BoF. Analyses of muscle tissues and viscera from the affected salmon indicated that any portion would not be a health hazard if consumed. 相似文献
46.
Rampant horizontal transfer and duplication of rubisco genes in eubacteria and plastids 总被引:14,自引:2,他引:14
Previous work has shown that molecular phylogenies of plastids,
cyanobacteria, and proteobacteria based on the rubisco (ribulose-1,5-
bisphosphate carboxylase/oxygenase) genes rbcL and rbcS are incongruent
with molecular phylogenies based on other genes and are also incompatible
with structural and biochemical information. Although it has been much
speculated that this is the consequence of a single horizontal gene
transfer (of a proteobacterial or mitochondrial rubisco operon into
plastids of rhodophytic and chromophytic algae), neither this hypothesis
nor the alternative hypothesis of ancient gene duplication have been
examined in detail. We have conducted phylogenetic analyses of all
available bacterial rbcL sequences, and representative plastid sequences,
in order to explore these alternative hypothesis and fully examine the
complexity of rubisco gene evolution. The rbcL phylogeny reveals a
surprising number of gene relationships that are fundamentally incongruent
with organismal relationships as inferred from multiple lines of other
molecular evidence. On the order of six horizontal gene transfers are
implied by the form I (L8S8) rbcL phylogeny, two between cyanobacteria and
proteobacteria, one between proteobacteria and plastids, and three within
proteobacteria. Alternatively, a single ancient duplication of the form I
rubisco operon, followed by repeated and pervasive differential loss of one
operon or the other, would account for much of this incongruity. In all
probability, the rubisco operon has undergone multiple events of both
horizontal gene transfer and gene duplication in different lineages.
相似文献
47.
Richard A Stabler Lisa F Dawson Petra CF Oyston Richard W Titball Jim Wade Jason Hinds Adam A Witney Brendan W Wren 《BMC microbiology》2008,8(1):177
Background
Human and animal health is constantly under threat by emerging pathogens that have recently acquired genetic determinants that enhance their survival, transmissibility and virulence. We describe the construction and development of an Active Surveillance of Pathogens (ASP) oligonucleotide microarray, designed to 'actively survey' the genome of a given bacterial pathogen for virulence-associated genes. 相似文献48.
49.
Vincenzo Trotta Federico CF Calboli Marcello Ziosi Daniela Guerra Maria C Pezzoli Jean R David Sandro Cavicchi 《BMC evolutionary biology》2006,6(1):67
Background
Populations of Drosophila melanogaster show differences in many morphometrical traits according to their geographic origin. Despite the widespread occurrence of these differences in more than one Drosophila species, the actual selective mechanisms controlling the genetic basis of such variation are not fully understood. Thermal selection is considered to be the most likely cause explaining these differences. 相似文献50.