全文获取类型
收费全文 | 161篇 |
免费 | 7篇 |
专业分类
168篇 |
出版年
2023年 | 1篇 |
2022年 | 2篇 |
2021年 | 8篇 |
2018年 | 1篇 |
2017年 | 2篇 |
2016年 | 4篇 |
2015年 | 6篇 |
2014年 | 11篇 |
2013年 | 13篇 |
2012年 | 17篇 |
2011年 | 13篇 |
2010年 | 12篇 |
2009年 | 7篇 |
2008年 | 8篇 |
2007年 | 3篇 |
2006年 | 5篇 |
2005年 | 4篇 |
2004年 | 6篇 |
2003年 | 5篇 |
2002年 | 5篇 |
2001年 | 2篇 |
2000年 | 3篇 |
1999年 | 3篇 |
1998年 | 1篇 |
1997年 | 2篇 |
1996年 | 1篇 |
1995年 | 3篇 |
1992年 | 5篇 |
1991年 | 1篇 |
1988年 | 4篇 |
1987年 | 1篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1977年 | 1篇 |
1974年 | 1篇 |
1968年 | 3篇 |
1966年 | 2篇 |
排序方式: 共有168条查询结果,搜索用时 0 毫秒
71.
72.
Maganga Sambo Tiziana Lembo Sarah Cleaveland Heather M. Ferguson Lwitiko Sikana Cleophas Simon Honorati Urassa Katie Hampson 《PLoS neglected tropical diseases》2014,8(12)
Background
Despite being entirely preventable, canine rabies still kills 55,000 people/year in developing countries. Information about local beliefs and practices can identify knowledge gaps that may affect prevention practices and lead to unnecessary deaths.Methodology/Principal Findings
We investigated knowledge, attitudes and practices related to rabies and its prevention and control amongst a cross-section of households (n = 5,141) in urban and rural areas of central, southern and northern Tanzania. Over 17% of respondents owned domestic dogs (average of 2.3 dogs/household),>95% had heard about rabies, and>80% knew that rabies is transmitted through dog bites. People who (1) had greater education, (2) originated from areas with a history of rabies interventions, (3) had experienced exposure by a suspect rabid animal, (4) were male and (5) owned dogs were more likely to have greater knowledge about the disease. Around 80% of respondents would seek hospital treatment after a suspect bite, but only 5% were aware of the need for prompt wound cleansing after a bite. Although>65% of respondents knew of dog vaccination as a means to control rabies, only 51% vaccinated their dogs. Determinants of dog vaccination included (1) being a male-headed household, (2) presence of children, (3) low economic status, (4) residing in urban areas, (5) owning livestock, (6) originating from areas with rabies interventions and (7) having purchased a dog. The majority of dog-owning respondents were willing to contribute no more than US$0.31 towards veterinary services.Conclusions/Significance
We identified important knowledge gaps related to, and factors influencing the prevention and control of rabies in Tanzania. Increasing knowledge regarding wound washing, seeking post-exposure prophylaxis and the need to vaccinate dogs are likely to result in more effective prevention of rabies; however, greater engagement of the veterinary and medical sectors is also needed to ensure the availability of preventative services. 相似文献73.
M Teruel F J Ruíz-Ruano J A Marchal A Sánchez J Cabrero J PM Camacho F Perfectti 《Heredity》2014,112(5):531-542
Wide arrays of repetitive DNA sequences form an important part of eukaryotic genomes. These repeats appear to evolve as coherent families, where repeats within a family are more similar to each other than to other orthologous representatives in related species. The continuous homogenization of repeats, through selective and non-selective processes, is termed concerted evolution. Ascertaining the level of variation between repeats is crucial to determining which evolutionary model best explains the homogenization observed for these sequences. Here, for the grasshopper Eyprepocnemis plorans, we present the analysis of intragenomic diversity for two repetitive DNA sequences (a satellite DNA (satDNA) and the 45S rDNA) resulting from the independent microdissection of several chromosomes. Our results show different homogenization patterns for these two kinds of paralogous DNA sequences, with a high between-chromosome structure for rDNA but no structure at all for the satDNA. This difference is puzzling, considering the adjacent localization of the two repetitive DNAs on paracentromeric regions in most chromosomes. The disparate homogenization patterns detected for these two repetitive DNA sequences suggest that several processes participate in the concerted evolution in E. plorans, and that these mechanisms might not work as genome-wide processes but rather as sequence-specific ones. 相似文献
74.
75.
Jacky Woo Michel PM Vierboom Hakju Kwon Debra Chao Shiming Ye Jianmin Li Karen Lin Irene Tang Nicole A Belmar Taymar Hartman Elia Breedveld Vladimir Vexler Bert A ‘t Hart Debbie A Law Gary C Starling 《Arthritis research & therapy》2013,15(6):R207
Introduction
Targeting the CD20 antigen has been a successful therapeutic intervention in the treatment of rheumatoid arthritis (RA). However, in some patients with an inadequate response to anti-CD20 therapy, a persistence of CD20- plasmablasts is noted. The strong expression of CD319 on CD20- plasmablast and plasma cell populations in RA synovium led to the investigation of the potential of CD319 as a therapeutic target.Methods
PDL241, a novel humanized IgG1 monoclonal antibody (mAb) to CD319, was generated and examined for its ability to inhibit immunoglobulin production from plasmablasts and plasma cells generated from peripheral blood mononuclear cells (PBMC) in the presence and absence of RA synovial fibroblasts (RA-SF). The in vivo activity of PDL241 was determined in a human PBMC transfer into NOD scid IL-2 gamma chain knockout (NSG) mouse model. Finally, the ability of PDL241 to ameliorate experimental arthritis was evaluated in a collagen-induced arthritis (CIA) model in rhesus monkeys.Results
PDL241 bound to plasmablasts and plasma cells but not naïve B cells. Consistent with the binding profile, PDL241 inhibited the production of IgM from in vitro PBMC cultures by the depletion of CD319+ plasmablasts and plasma cells but not B cells. The activity of PDL241 was dependent on an intact Fc portion of the IgG1 and mediated predominantly by natural killer cells. Inhibition of IgM production was also observed in the human PBMC transfer to NSG mouse model. Treatment of rhesus monkeys in a CIA model with PDL241 led to a significant inhibition of anti-collagen IgG and IgM antibodies. A beneficial effect on joint related parameters, including bone remodeling, histopathology, and joint swelling was also observed.Conclusions
The activity of PDL241 in both in vitro and in vivo models highlights the potential of CD319 as a therapeutic target in RA. 相似文献76.
Ana PM Oliveira Rosana Gentile Arnaldo Maldonado Júnior Eduardo J Lopes Torres Silvana C Thiengo 《Memórias do Instituto Oswaldo Cruz》2015,110(6):739-744
The aim of this study was to analyse the infection dynamics ofAngiostrongylus
cantonensis in its possible intermediate hosts over two years in an urban
area in the state of Rio de Janeiro where the presence ofA.
cantonensis had been previously recorded in molluscs. Four of the seven
mollusc species found in the study were exotic.Bradybaena similaris
was the most abundant, followed byAchatina fulica,
Streptaxis sp., Subulina octona,
Bulimulus tenuissimus, Sarasinula linguaeformis
and Leptinaria unilamellata. Only A. fulica
and B. similaris were parasitised by A.
cantonensis and both presented co-infection with other helminths. The
prevalence of A. cantonensisin A. fulica was more
than 50% throughout the study. There was an inverse correlation between the
population size ofA. fulica and the prevalence of A.
cantonensis and abundance of the latter was negatively related to
rainfall. The overall prevalence of A. cantonensis in B.
similariswas 24.6%. A. fulica was the most important
intermediary host of A. cantonensis in the studied area
andB. similaris was secondary in importance for A.
cantonensis transmission dynamics. 相似文献
77.
Beatriz Salvador Nicole R. Sexton Ricardo Carrion Jr. Jerritt Nunneley Jean L. Patterson Imke Steffen Kai Lu Marcus O. Muench David Lembo Graham Simmons 《Journal of virology》2013,87(6):3295-3304
Filoviruses are the cause of severe hemorrhagic fever in human and nonhuman primates. The envelope glycoprotein (GP), responsible for both receptor binding and fusion of the virus envelope with the host cell membrane, has been demonstrated to interact with multiple molecules in order to enhance entry into host cells. Here we have demonstrated that filoviruses utilize glycosaminoglycans, and more specifically heparan sulfate proteoglycans, for their attachment to host cells. This interaction is mediated by GP and does not require the presence of the mucin domain. Both the degree of sulfation and the structure of the carbohydrate backbone play a role in the interaction with filovirus GPs. This new step of filovirus interaction with host cells can potentially be a new target for antiviral strategies. As such, we were able to inhibit filovirus GP-mediated infection using carrageenan, a broad-spectrum microbicide that mimics heparin, and also using the antiviral dendrimeric peptide SB105-A10, which interacts with heparan sulfate, antagonizing the binding of the virus to cells. 相似文献
78.
Replacement of K-Ras with H-Ras supports normal embryonic development despite inducing cardiovascular pathology in adult mice 总被引:1,自引:0,他引:1
Potenza N Vecchione C Notte A De Rienzo A Rosica A Bauer L Affuso A De Felice M Russo T Poulet R Cifelli G De Vita G Lembo G Di Lauro R 《EMBO reports》2005,6(5):432-437
Ras proteins are highly related GTPases that have key roles in regulating growth, differentiation and tumorigenesis. Gene-targeting experiments have shown that, out of the three mammalian ras genes, only K-ras is essential for normal mouse embryogenesis, and that mice deprived of H-ras and/or N-ras show no major phenotype. We generated mice (HrasKI) in which the K-ras gene had been modified to encode H-Ras protein. HrasKI mice produce undetectable amounts of K-Ras but-in contrast to mice homozygous for a null K-ras allele-they are born at the expected mendelian frequency, indicating that H-Ras can be substituted for K-Ras in embryonic development. However, adult HrasKI mice show dilated cardiomyopathy associated with arterial hypertension. Our results show that K-Ras can be replaced by H-Ras in its essential function in embryogenesis, and indicate that K-Ras has a unique role in cardiovascular homeostasis. 相似文献
79.
Raffaele Capasso Gabriella Aviello Francesco Capasso Francesco Savino Angelo A. Izzo Francesca Lembo Francesca Borrelli 《Phytomedicine》2009,16(9):839-844
Breastfeeding is widely acknowledged to have important health benefits for infants and mothers. Milk thistle (Silybum marianum fruits) has been recently proposed to be used by nursing mothers for stimulating milk production; however, the mode of action of this herbal drug is still unknown. In this paper, we have evaluated the effect of a micronized standardized extract of S. marianum (Silymarin BIO-C®=Piùlatte®) on the serum levels of prolactin in female rats. A 14-day treatment with Silymarin BIO-C® (25–200 mg/kg, given orally) increased, in a dose dependent manner, the serum prolactin levels. Moreover, after a 66-day discontinuation of Silymarin BIO-C® treatment, prolactin levels were still significantly elevated although we observed a trend to decrease that was counteracted by a further 7-day treatment with Silymarin BIO-C®. Bromocriptine, a dopamine D2 receptor agonist, (1–10 mg/kg, os) significantly and in a dose dependent manner, reduced the serum prolactin levels; bromocriptine, at the dose of 1 mg/kg, significantly reduced the high serum prolactin levels induced by Silymarin BIO-C®. In conclusion, we have shown that an extract from S. marianum fruits significantly increases circulating prolactin levels in female rats; this effect seems to involve, at least in part, dopamine D2 receptors. 相似文献
80.
Fabrizio Villa Ryo Fujisawa Johanna Ainsworth Kohei Nishimura Michael LieALing Georges Lacaud Karim PM Labib 《EMBO reports》2021,22(3)
The eukaryotic replisome is disassembled in each cell cycle, dependent upon ubiquitylation of the CMG helicase. Studies of Saccharomyces cerevisiae, Caenorhabditis elegans and Xenopus laevis have revealed surprising evolutionary diversity in the ubiquitin ligases that control CMG ubiquitylation, but regulated disassembly of the mammalian replisome has yet to be explored. Here, we describe a model system for studying the ubiquitylation and chromatin extraction of the mammalian CMG replisome, based on mouse embryonic stem cells. We show that the ubiquitin ligase CUL2LRR1 is required for ubiquitylation of the CMG‐MCM7 subunit during S‐phase, leading to disassembly by the p97 ATPase. Moreover, a second pathway of CMG disassembly is activated during mitosis, dependent upon the TRAIP ubiquitin ligase that is mutated in primordial dwarfism and mis‐regulated in various cancers. These findings indicate that replisome disassembly in diverse metazoa is regulated by a conserved pair of ubiquitin ligases, distinct from those present in other eukaryotes. 相似文献