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排序方式: 共有223条查询结果,搜索用时 78 毫秒
41.
Clément Lagrue Robert Poulin Devon B. Keeney 《Evolution; international journal of organic evolution》2009,63(6):1417-1426
Theoretical models predict that genetic relatedness affects the competition within and between parasite clonal groups sharing a common host. Here, we studied natural and experimental multiple infections of the trematode Coitocaecum parvum in its intermediate host. We focused on the effects of clonality on the life-history strategy of parasites competing for resources. Coitocaecum parvum can either delay maturation until its amphipod host is ingested by a definitive host, or adopt a progenetic strategy and reproduce inside the amphipod. Within a common host, clonal parasites were more likely to adopt identical life-history strategies than different genetic clones, both in natural and experimental infections. However, when timing of infection and other factors were controlled experimentally, parasites sharing a host were likely to adopt identical strategies regardless of their clonal identity, although pairs of clones were more likely to adopt progenesis than pairs of nonclones. The asymmetries in relative size and egg production between coinfecting parasites adopting the same life-history strategy were slightly, but not significantly, higher between different clones than identical clones. Our results suggest that the dynamics of competition between coinfecting parasites, although influenced by numerous external factors, is also modulated by genetic relatedness among parasites. 相似文献
42.
Zili Zhai Devon M. Haney Lankun Wu Avery K. Solco Patricia A. Murphy Eve S. Wurtele Marian L. Kohut Joan E. Cunnick 《Phytomedicine》2009,16(6-7):669-678
Healing of open skin wounds begins with an inflammatory response. Restraint stress has been well documented to delay wound closure, partially via glucocorticoid (GC)-mediated immunosuppression of inflammation. Echinacea, a popular herbal immunomodulator, is purported to be beneficial for wound healing. To test the hypothesis, an alcohol extract of E. pallida was administrated orally to mice for 3 days prior to, and 4 days post wounding with a dermal biopsy on the dorsum. Concominantly, mice were exposed to 3 cycles of daily restraint stress prior to, and 4 cycles post wounding. Echinacea accelerated wound closure in the stressed mice, but had no apparent wound healing effect for the non-stressed mice when compared to their respective controls. To test if the positive healing effect is through modulation of GC release, plasma corticosterone concentrations were measured in unwounded mice treated with restraint stress and the herbal extract for 4 days. Plasma GC in restraint stressed mice gavaged with Echinacea was not different from mice treated with restraint only, but was increased compared to the vehicle control. This data suggests that the improved wound healing effect of Echinacea in stressed mice is not mediated through modulation of GC signaling. 相似文献
43.
Dinesh C. Soares Paul N. Barlow David J. Porteous Rebecca S. Devon 《Journal of molecular modeling》2009,15(2):113-122
Defects in the human ALS2 gene, which encodes the 1,657-amino-acid residue protein alsin, are linked to several related motor neuron diseases. We created
a structural model for the N-terminal 690-residue region of alsin through comparative modelling based on regulator of chromosome
condensation 1 (RCC1). We propose that this alsin region contains seven RCC1-like repeats in a seven-bladed beta-propeller
structure. The propeller is formed by a double clasp arrangement containing two segments (residues 1–218 and residues 525–690).
The 306-residue insert region, predicted to lie within blade 5 and to be largely disordered, is poorly conserved across species.
Surface patches of evolutionary conservation probably indicate locations of binding sites. Both disease-causing missense mutations—Cys157Tyr
and Gly540Glu—are buried in the propeller and likely to be structurally disruptive. This study aids design of experimental
studies by highlighting the importance of construct length, will enhance interpretation of protein–protein interactions, and
enable rational site-directed mutagenesis.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
44.
Genetic association of the antiviral restriction factor TRIM5alpha with human immunodeficiency virus type 1 infection 下载免费PDF全文
Speelmon EC Livingston-Rosanoff D Li SS Vu Q Bui J Geraghty DE Zhao LP McElrath MJ 《Journal of virology》2006,80(5):2463-2471
The innate antiviral factor TRIM5alpha restricts the replication of some retroviruses through its interaction with the viral capsid protein, leading to abortive infection. While overexpression of human TRIM5alpha results in modest restriction of human immunodeficiency virus type 1 (HIV-1), this inhibition is insufficient to block productive infection of human cells. We hypothesized that polymorphisms within TRIM5 may result in increased restriction of HIV-1 infection. We sequenced the TRIM5 gene (excluding exon 5) and the 4.8-kb 5' putative regulatory region in genomic DNA from 110 HIV-1-infected subjects and 96 exposed seronegative persons, along with targeted gene sequencing in a further 30 HIV-1-infected individuals. Forty-eight single nucleotide polymorphisms (SNPs), including 20 with allele frequencies of >1.0%, were identified. Among these were two synonymous and eight nonsynonymous coding polymorphisms. We observed no association between TRIM5 polymorphism in HIV-1-infected subjects and their set-point viral load after acute infection, although one TRIM5 haplotype was weakly associated with more rapid CD4(+) T-cell loss. Importantly, a TRIM5 haplotype containing the nonsynonymous SNP R136Q showed increased frequency among HIV-1-infected subjects relative to exposed seronegative persons, with an odds ratio of 5.49 (95% confidence interval = 1.83 to 16.45; P = 0.002). Nonetheless, we observed no effect of individual TRIM5alpha nonsynonymous mutations on the in vitro HIV-1 susceptibility of CD4(+) T cells. Therefore, any effect of TRIM5alpha polymorphism on HIV-1 infection in primary lymphocytes may depend on combinations of SNPs or on DNA sequences in linkage disequilibrium with the TRIM5alpha coding sequence. 相似文献
45.
Leigh Perreault Bryan C. Bergman Devon M. Hunerdosse Robert H. Eckel 《Obesity (Silver Spring, Md.)》2010,18(11):2093-2100
Whether sex differences in intramuscular triglyceride (IMTG) metabolism underlie sex differences in the progression to diabetes are unknown. Therefore, the current study examined IMTG concentration and fractional synthesis rate (FSR) in obese men and women with normal glucose tolerance (NGT) vs. those with prediabetes (PD). PD (n = 13 men and 7 women) and NGT (n = 7 men and 12 women) groups were matched for age and anthropometry. Insulin action was quantified using a hyperinsulinemic‐euglycemic clamp with infusion of [6,6?2H2]‐glucose. IMTG concentration was measured by gas chromatography/mass spectrometry (GC/MS) and FSR by GC/combustion isotope ratio MS (C‐IRMS), from muscle biopsies taken after infusion of [U?13C]palmitate during 4 h of rest. In PD men, the metabolic clearance rate (MCR) of glucose was lower during the clamp (4.71 ± 0.77 vs. 8.62 ± 1.26 ml/kg fat‐free mass (FFM)/min, P = 0.04; with a trend for lower glucose rate of disappearance (Rd), P = 0.07), in addition to higher IMTG concentration (41.2 ± 5.0 vs. 21.2 ± 3.4 µg/mg dry weight, P ≤ 0.01), lower FSR (0.21 ± 0.03 vs. 0.42 ± 0.06 %/h, P ≤ 0.01), and lower oxidative capacity (P = 0.03) compared to NGT men. In contrast, no difference in Rd, IMTG concentration, or FSR was seen in PD vs. NGT women. Surprisingly, glucose Rd during the clamp was not different between NGT men and women (P = 0.25) despite IMTG concentration being higher (42.6 ± 6.1 vs. 21.2 ± 3.4 µg/mg dry weight, P = 0.03) and FSR being lower (0.23 ± 0.04 vs. 0.42 ± 0.06 %/h, P = 0.02) in women. Alterations in IMTG metabolism relate to diminished insulin action in men, but not women, in the progression toward diabetes. 相似文献
46.
Muthumani K Shedlock DJ Choo DK Fagone P Kawalekar OU Goodman J Bian CB Ramanathan AA Atman P Tebas P Chattergoon MA Choo AY Weiner DB 《Journal of immunology (Baltimore, Md. : 1950)》2011,187(6):2932-2943
Recent evidence demonstrates that HIV-1 infection leads to the attenuation of cellular immune responses, which has been correlated with the increased expression of programmed death (PD)-1 on virus-specific CD8(+) T cells. PD-1 is induced upon T cell activation, and its prolonged expression facilitates CD8(+) T cell inhibitory signals when bound to its B7 family ligands, PD-ligand (L)1/2, which are expressed on APCs. Importantly, early reports demonstrated that blockade of the PD-1/PD-L interaction by Abs may help to counter the development of immune exhaustion driven by HIV viral persistence. To better understand the regulation of the PD-1 pathway during HIV infection, we examined the ability of the virus to induce PD-L expression on macrophages and dendritic cells. We found a direct relationship between the infection of APCs and the expression of PD-L1 in which virus-mediated upregulation induced a state of nonresponsiveness in uninfected HIV-specific T cells. Furthermore, this exhaustion phenotype was revitalized by the blockade of PD-L1, after which T cells regained their capacity for proliferation and the secretion of proinflammatory cytokines IFN-γ, IL-2, and IL-12 upon restimulation. In addition, we identify a critical role for the PI3K/serine-threonine kinase signaling pathway in PD-L1 upregulation of APCs by HIV, because inhibition of these intracellular signal transducer enzymes significantly reduced PD-L1 induction by infection. These data identify a novel mechanism by which HIV exploits the immunosuppressive PD-1 pathway and suggest a new role for virus-infected cells in the local corruption of immune responses required for viral suppression. 相似文献
47.
Alexander W Wyatt Fan Mo Kendric Wang Brian McConeghy Sonal Brahmbhatt Lina Jong Devon M Mitchell Rebecca L Johnston Anne Haegert Estelle Li Janet Liew Jake Yeung Raunak Shrestha Anna V Lapuk Andrew McPherson Robert Shukin Robert H Bell Shawn Anderson Jennifer Bishop Antonio Hurtado-Coll Hong Xiao Arul M Chinnaiyan Rohit Mehra Dong Lin Yuzhuo Wang Ladan Fazli Martin E Gleave Stanislav V Volik Colin C Collins 《Genome biology》2014,15(8)
48.
Devon Pendlebury Ruiying Wang Rachel D. Henin Alexandra Hockla Alexei S. Soares Benjamin J. Madden Marat D. Kazanov Evette S. Radisky 《The Journal of biological chemistry》2014,289(47):32783-32797
Mesotrypsin is an isoform of trypsin that is uniquely resistant to polypeptide trypsin inhibitors and can cleave some inhibitors rapidly. Previous studies have shown that the amyloid precursor protein Kunitz protease inhibitor domain (APPI) is a specific substrate of mesotrypsin and that stabilization of the APPI cleavage site in a canonical conformation contributes to recognition by mesotrypsin. We hypothesized that other proteins possessing potential cleavage sites stabilized in a similar conformation might also be mesotrypsin substrates. Here we evaluated a series of candidate substrates, including human Kunitz protease inhibitor domains from amyloid precursor-like protein 2 (APLP2), bikunin, hepatocyte growth factor activator inhibitor type 2 (HAI2), tissue factor pathway inhibitor-1 (TFPI1), and tissue factor pathway inhibitor-2 (TFPI2), as well as E-selectin, an unrelated protein possessing a potential cleavage site displaying canonical conformation. We find that Kunitz domains within APLP2, bikunin, and HAI2 are cleaved by mesotrypsin with kinetic profiles of specific substrates. TFPI1 and TFPI2 Kunitz domains are cleaved less efficiently by mesotrypsin, and E-selectin is not cleaved at the anticipated site. Cocrystal structures of mesotrypsin with HAI2 and bikunin Kunitz domains reveal the mode of mesotrypsin interaction with its canonical substrates. Our data suggest that major determinants of mesotrypsin substrate specificity include sequence preferences at the P1 and P′2 positions along with conformational stabilization of the cleavage site in the canonical conformation. Mesotrypsin up-regulation has been implicated previously in cancer progression, and proteolytic clearance of Kunitz protease inhibitors offers potential mechanisms by which mesotrypsin may mediate pathological effects in cancer. 相似文献
49.
Nicole C. Thunes Rachel A. Conrad Haitham H. Mohammed Yongtao Zhu Paul Barbier Jason P. Evenhuis David Perez-Pascual Jean-Marc Ghigo Ryan S. Lipscomb John R. Schneider Nan Li Devon H. Erbes Clayton Birkett Benjamin R. LaFrentz Timothy J. Welch Mark J. McBride 《Applied and environmental microbiology》2022,88(3)
50.
Pamela E. Ventola Devon R. Oosting Cara M. Keifer Hannah E. Friedman 《The Yale journal of biology and medicine》2015,88(1):37-44
There is a growing literature on children with autism spectrum disorder (ASD) who respond favorably to behavioral treatment, which is often termed “optimal outcome.” Rates and definitions of optimal outcome vary widely. The current case series describes an empirically validated behavioral treatment approach called Pivotal Response Treatment (PRT). We present two preschool-aged children who received an intensive course of PRT and seem to be on a trajectory toward potential optimal outcome. Understanding response to treatment and predictors of response is crucial, not necessarily to predict who may succeed, but to individualize medicine and match children with customized treatment programs that will be best tailored to their unique and varied needs. 相似文献