全文获取类型
收费全文 | 96篇 |
免费 | 12篇 |
专业分类
108篇 |
出版年
2022年 | 1篇 |
2021年 | 2篇 |
2018年 | 1篇 |
2017年 | 1篇 |
2016年 | 4篇 |
2015年 | 5篇 |
2014年 | 4篇 |
2013年 | 6篇 |
2012年 | 9篇 |
2011年 | 4篇 |
2010年 | 5篇 |
2009年 | 2篇 |
2008年 | 9篇 |
2007年 | 4篇 |
2006年 | 3篇 |
2004年 | 4篇 |
2003年 | 6篇 |
2002年 | 4篇 |
2001年 | 3篇 |
2000年 | 4篇 |
1999年 | 5篇 |
1998年 | 6篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1991年 | 2篇 |
1986年 | 1篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1979年 | 1篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1973年 | 1篇 |
1969年 | 1篇 |
排序方式: 共有108条查询结果,搜索用时 15 毫秒
51.
Muhammad Yunus Amran Jun Fujii Satoshi O. Suzuki Glynis L. Kolling Sharon Y. A. M. Villanueva Mosaburo Kainuma Hideyuki Kobayashi Hideko Kameyama Shin-ichi Yoshida 《PloS one》2013,8(3)
A large outbreak of Shiga toxin (Stx)-producing enteroaggregative Escherichia coli (EAEC) O104:H4 occurred in northern Germany. From this outbreak, at least 900 patients developed hemolytic uremic syndrome (HUS), resulting in more than 50 deaths. Thirty percent of the HUS patients showed encephalopathy. We previously established a mouse model with encephalopathy associated with blood brain barrier (BBB) damage after oral infection with the Shiga toxin (Stx) 2c-producing Escherichia coli O157: H- strain ( E32511). In this model, we detected high expression of the Stx receptor synthase enzyme, glycosphingolipid globotriaosylceramide (Gb3) synthase, in endothelial cells (ECs) and neurons in the reticular formation of the medulla oblongata by in situ hybridization. Caspase-3 was activated in neurons in the reticular formation of the medulla oblongata and the anterior horn of the spinal cord. Astrocytes (ASTs) were activated in the medulla oblongata and spinal cord, and a decrease in aquaporin 4 around the ECs suggested that BBB integrity was compromised directly by Stx2c or through the activation of ASTs. We also report the effectiveness of azithromycin (AZM) in our model. Moreover, AZM strongly inhibited the release of Stx2c from E32511 in vitro. E32511相似文献
52.
Morphological features of a collection of unknown-age wild kiwi (Apteryx mantelli) embryos from early development to point of hatch are described. Using these features, we assign developmental stages to each embryo and compare the progress of development to similar-staged ostrich (Struthio camelus) and chicken (Gallus gallus) embryos. Two ageing schemes for the kiwi embryos are developed by comparing measurements of their hindlimb segments, bills and crown–rump lengths with those of ostrich and chicken embryos at various stages of development. One of the 20 kiwi embryos was of known age. Both the ostrich model and the chicken model gave identical predictions for the marker and four other embryos. Developmental timing of some features differed between all three species, most markedly in the bill, with growth in the kiwi bill being relatively faster to achieve its larger relative and absolute size at hatch. 相似文献
53.
54.
55.
Jan Štefka Paquita EA Hoeck Lukas F Keller Vincent S Smith 《BMC evolutionary biology》2011,11(1):1-19
Background
Parasites are evolutionary hitchhikers whose phylogenies often track the evolutionary history of their hosts. Incongruence in the evolutionary history of closely associated lineages can be explained through a variety of possible events including host switching and host independent speciation. However, in recently diverged lineages stochastic population processes, such as retention of ancestral polymorphism or secondary contact, can also explain discordant genealogies, even in fully co-speciating taxa. The relatively simple biogeographic arrangement of the Galápagos archipelago, compared with mainland biomes, provides a framework to identify stochastic and evolutionary informative components of genealogic data in these recently diverged organisms.Results
Mitochondrial DNA sequences were obtained for four species of Galápagos mockingbirds and three sympatric species of ectoparasites - two louse and one mite species. These data were complemented with nuclear EF1α sequences in selected samples of parasites and with information from microsatellite loci in the mockingbirds. Mitochondrial sequence data revealed differences in population genetic diversity between all taxa and varying degrees of topological congruence between host and parasite lineages. A very low level of genetic variability and lack of congruence was found in one of the louse parasites, which was excluded from subsequent joint analysis of mitochondrial data. The reconciled multi-species tree obtained from the analysis is congruent with both the nuclear data and the geological history of the islands.Conclusions
The gene genealogies of Galápagos mockingbirds and two of their ectoparasites show strong phylogeographic correlations, with instances of incongruence mostly explained by ancestral genetic polymorphism. A third parasite genealogy shows low levels of genetic diversity and little evidence of co-phylogeny with their hosts. These differences can mostly be explained by variation in life-history characteristics, primarily host specificity and dispersal capabilities. We show that pooling genetic data from organisms living in close ecological association reveals a more accurate phylogeographic history for these taxa. Our results have implications for the conservation and taxonomy of Galápagos mockingbirds and their parasites. 相似文献56.
Recent identification of the modular CLS motifs responsible for cyclins A and E localization on centrosomes has revealed a tight linkage between the nuclear and centrosomal cycles. These G1/S cyclins must localize on the centrosome in order for DNA replication to occur in the nucleus, whereas essential DNA replication factors also function on the centrosome to prevent centrosome overduplication. Both events are dependent on the presence of an intact CLS within each cyclin. Here we compare the cyclins A and E CLSs at the structural and functional levels and identify a new cyclin A CLS mutant that disrupts all CLS functions and reduces the affinity of cyclin A for Cdk2. Analysis of interactions of the CLS motif within the cyclin molecules highlights the importance of the cyclin CBOX1 region for Cdk2 binding.Key words: cyclin A, cyclin E, Cdk2, centrosome, CLS, PSTAIRE, DNA synthesis 相似文献
57.
Karen EA Burns Clarence Chant Orla Smith Brian Cuthbertson Robert Fowler Deborah J Cook Peter Kruger Steve Webb Jamal Alhashemi Guillermo Dominguez-Cherit Carlos Zala Gordon D Rubenfeld John C Marshall 《Trials》2011,12(1):1-10
Background
The Vaccine Assessment using Linked Data (VALiD) trial compared opt-in and opt-out parental consent for a population-based childhood vaccine safety surveillance program using data linkage. A subsequent telephone interview of all households enrolled in the trial elicited parental intent regarding the return or non-return of reply forms for opt-in and opt-out consent. This paper describes the rationale for the trial and provides an overview of the design and methods.Methods/Design
Single-centre, single-blind, randomised controlled trial (RCT) stratified by firstborn status. Mothers who gave birth at one tertiary South Australian hospital were randomised at six weeks post-partum to receive an opt-in or opt-out reply form, along with information explaining data linkage. The primary outcome at 10 weeks post-partum was parental participation in each arm, as indicated by the respective return or non-return of a reply form (or via telephone or email response). A subsequent telephone interview at 10 weeks post-partum elicited parental intent regarding the return or non-return of the reply form, and attitudes and knowledge about data linkage, vaccine safety, consent preferences and vaccination practices. Enrolment began in July 2009 and 1,129 households were recruited in a three-month period. Analysis has not yet been undertaken. The participation rate and selection bias for each method of consent will be compared when the data are analysed.Discussion
The VALiD RCT represents the first trial of opt-in versus opt-out consent for a data linkage study that assesses consent preferences and intent compared with actual opting in or opting out behaviour, and socioeconomic factors. The limitations to generalisability are discussed.Trial registration
Australian New Zealand Clinical Trials Registry ACTRN12610000332022 相似文献58.
59.
Following addition of myxothiazol to antimycin-treated chromatophores from Rhodobacter sphaeroides poised at an ambient redox potential (E(h)) of approximately 300 mV, the amplitude of the flash-induced cytochrome c(1) oxidation in the ms range increased, indicating a decrease in the availability of electrons from the immediate donor to c(1), the Rieske iron-sulfur protein (ISP). Because the effect was seen only over the limited E(h) range, we conclude that it is due to a decrease in the apparent midpoint redox potential (E(m)) of the ISP by about 40 mV on addition of myxothiazol. This is in line with the change in E(m) previously seen in direct redox titrations. Our results show that the reduced ISP binds with quinone at the Q(o) site with a higher affinity than does the oxidized ISP. The displacement of ubiquinone by myxothiazol leads to elimination of this preferential binding of the ISP reduced form and results in a shift in the midpoint potential of ISP to a more negative value. A simple hypothesis to explain this effect is that myxothiazol prevents formation of hydrogen bond of ubiquinone with the reduced ISP. We conclude that all Q(o) site occupants (ubiquinone, UHDBT, stigmatellin) that form hydrogen bonds with the reduced ISP shift the apparent E(m) of the ISP in the same direction to more positive values. Inhibitors that bind in the domain of the Q(o) site proximal to heme b(L) (myxothiazol, MOA-stilbene) and displace ubiquinone from the site cause a decrease in E(m) of ISP. We present a new formalism for treatment of the relation between E(m) change and the binding constants involved, which simplifies analysis. Using this formalism, we estimated that binding free energies for hydrogen bond formation with the Q(o) site occupant, range from the largest value of approximately 23 kJ mol(-1) in the presence of stigmatellin (appropriate for the buried hydrogen bond shown by structures), to a value of approximately 3.5 kJ mol(-1) in the native complex. We discuss this range of values in the context of a model in which the native structure constrains the interaction of ISP with the Q(o) site occupant so as to favor dissociation and the faster kinetics of unbinding necessary for rapid turnover. 相似文献
60.
The purpose of this study was to elucidate the formation of crystal hydrates of niclosamide and to delineate the effect of
relative humidity on the crystal forms obtained from acetone and ethyl acetate. Recrystallization of niclosamide was performed
in the presence and absence of moisture. Two hydrates and their corresponding anhydrates were isolated. The hydrates obtained
by the process of recrystallization from acetone (Form I) and that obtained from ethyl acetate (Form II) were classified based
on differences in their dehydration profile, crystal structure, shape, and morphology. Crystals obtained in the absence of
moisture were unstable, and when exposed to the laboratory atmosphere transformed to their corresponding hydrates. Differential
scanning calorimetry thermograms indicate that Form I changes to an anhydrate at temperatures below 100°C, while Form II dehydrates
in a stepwise manner above, 140°C. This finding was further confirmed by thermogravimetric analysis. Dehydration of Form II
was accompanied by a loss of structural integrity, demonstrating that water molecules play an important role in maintaining
its crystal structure. Form I, Form II, and the anhydrate of Form II showed no significant moisture sorption over the entire
range of relative humidity. Although the anhydrate of Form I did not show any moisture uptake at low humidity, it converted
to the monohydrate at elevated relative humidity (>95%). All forms could be interconverted depending on the solvent and humidity
conditions. 相似文献