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31.
Hendrik Streeck Jonathan S. Jolin Ying Qi Bader Yassine-Diab Randall C. Johnson Douglas S. Kwon Marylyn M. Addo Chanson Brumme Jean-Pierre Routy Susan Little Heiko K. Jessen Anthony D. Kelleher Frederick M. Hecht Rafick-Pierre Sekaly Eric S. Rosenberg Bruce D. Walker Mary Carrington Marcus Altfeld 《Journal of virology》2009,83(15):7641-7648
Primary HIV-1 infection (PHI) is marked by a flu-like syndrome and high levels of viremia that decrease to a viral set point with the first emergence of virus-specific CD8+ T-cell responses. Here, we investigated in a large cohort of 527 subjects the immunodominance pattern of the first virus-specific cytotoxic T-lymphocyte (CTL) responses developed during PHI in comparison to CTL responses in chronic infection and demonstrated a distinct relationship between the early virus-specific CTL responses and the viral set point, as well as the slope of CD4+ T-cell decline. CTL responses during PHI followed clear hierarchical immunodominance patterns that were lost during the transition to chronic infection. Importantly, the immunodominance patterns of human immunodeficiency virus type 1 (HIV-1)-specific CTL responses detected in primary, but not in chronic, HIV-1 infection were significantly associated with the subsequent set point of viral replication. Moreover, the preservation of the initial CD8+ T-cell immunodominance patterns from the acute into the chronic phase of infection was significantly associated with slower CD4+ T-cell decline. Taken together, these data show that the specificity of the initial CTL response to HIV is critical for the subsequent control of viremia and have important implications for the rational selection of antigens for future HIV-1 vaccines.In the first weeks after human immunodeficiency virus type 1 (HIV-1) acquisition, viral loads peak at high levels, accompanied by a flu-like syndrome (15). A rapid depletion of the CD4+ T-cell population occurs during this acute infection, in particular, within the gastrointestinal tract-associated lymphoid tissue (6, 19, 20), marking a nonrecoverable scar on the immune system. With the resolution of the clinical syndromes, viral loads decrease to a set point, which persists at this level for months to years until progressive CD4+ T-cell decline results in the onset of AIDS. It has been shown that the initial viral set point following primary infection is a very strong predictor of the disease-free period until the onset of AIDS (18, 21, 22).The initial decrease in the viral load during primary HIV-1 infection (PHI) is temporally associated with the first emergence of virus-specific CD8+ T-cell responses, and several studies have provided strong evidence that HIV-1-specific CD8+ T-cell responses are capable of controlling viral replication (5, 16, 24, 25, 27, 31, 33). However, significant numbers of virus-specific CD8+ T cells are detectable both in chronically infected individuals who progress rapidly to AIDS and in those who do not experience HIV-1 disease progression for decades (1, 11), and the characteristics that define a protective HIV-1-specific CD8+ T-cell response are not known. In particular, the level of control over viral replication is not predicted by the overall breadth, magnitude, or function of virus-specific CD8+ T-cell responses in chronic HIV-1 infection (1, 4, 11, 26, 28).Here, we demonstrate in a large cohort of individuals identified during PHI that immunodominance patterns of virus-specific CD8+ T-cell responses detected in PHI, but not in chronic HIV-1 infection, are strongly associated with the subsequent set point of viral replication. These data show that the specificity of the initial CD8+ T-cell response to HIV is critical for the subsequent control of viremia and have important implications for the rational selection of antigens for future HIV-1 vaccines. 相似文献
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34.
Three experiments were carried out to examine the consequences of concurrent infections with Ascaridia galli and Escherichia coli in chickens raised for table egg production. Characteristic pathological lesions including airsacculitis, peritonitis and/or polyserositis were seen in all groups infected with E. coli. Furthermore, a trend for increased mortality rates was observed in groups infected with both organisms which, however, could not be confirmed statistically. The mean worm burden was significantly lower in combined infection groups compared to groups infected only with A. galli. It was also shown that combined infections of E. coli and A. galli had an added significant negative impact on weight gain. 相似文献
35.
Thomas Galewski Marie-ka Tilak Sophie Sanchez Pascale Chevret Emmanuel Paradis Emmanuel JP Douzery 《BMC evolutionary biology》2006,6(1):80-17
Background
Mitochondrial and nuclear genes have generally been employed for different purposes in molecular systematics, the former to resolve relationships within recently evolved groups and the latter to investigate phylogenies at a deeper level. In the case of rapid and recent evolutionary radiations, mitochondrial genes like cytochrome b (CYB) are often inefficient for resolving phylogenetic relationships. One of the best examples is illustrated by Arvicolinae rodents (Rodentia; Muridae), the most impressive mammalian radiation of the Northern Hemisphere which produced voles, lemmings and muskrats. Here, we compare the relative contribution of a nuclear marker – the exon 10 of the growth hormone receptor (GHR) gene – to the one of the mitochondrial CYB for inferring phylogenetic relationships among the major lineages of arvicoline rodents. 相似文献36.
Alter G Hatzakis G Tsoukas CM Pelley K Rouleau D LeBlanc R Baril JG Dion H Lefebvre E Thomas R Côté P Lapointe N Routy JP Sékaly RP Conway B Bernard NF 《Journal of immunology (Baltimore, Md. : 1950)》2003,171(1):477-488
Both the magnitude and breadth of HIV-specific immunity were evaluated longitudinally on samples collected from six subjects starting highly active antiretroviral therapy (HAART) preseroconversion (group 1), 11 recently infected subjects starting HAART postseroconversion (group 2), five subjects starting HAART in the second half of the first year of infection (group 3), and six persons starting treatment in the chronic phase of infection (group 4). HIV-specific immunity was measured by IFN-gamma ELISPOT, detecting the frequency of cells responding to a panel of HLA-restricted HIV-1 peptides. Intracellular cytokine staining was used to detect the frequency of HIV-1 Gag p55-specific CD4(+) and CD8(+) T cells in a subset of participants. The magnitude and breadth of HIV-specific responses persisted in all group 1 subjects and in 5 of 11 (45%) group 2 subjects. Both of these parameters declined in 6 of 11 (55%) group 2 and in all group 3 and 4 individuals. All persons who maintained detectable numbers of HIV-1 Gag p55-specific CD4(+) and CD8(+) T cells after starting HAART preserved the intensity and breadth of their HIV-specific effector response. Our results show that HIV-specific immunity can be preserved even if HAART is initiated beyond the acute phase of infection. 相似文献
37.
38.
Previously, treatment of Tamm-Horsfall glycoprotein (THp) from different
donors with endo-beta-galactosidase has been shown to liberate a tetra- and
a Sd(a)-active pentasaccharide, concluding the presence of N-linked
carbohydrate chains containing additional N - acetyllactosamine units.
These type of oligosaccharides were not found in a detailed structure
elucidation of the carbohydrate moiety of THp of one male donor, suggesting
a donor-specific feature for these type of structures. Therefore, THp was
isolated from four healthy male donors and each subjected to
endo-beta-galactosidase treatment in order to release these tetra- and
Sd(a)-active pentasaccharide. Differences were observed in the total amount
of released tetra- and Sda-active pentasaccharide of the used donors (42,
470, 478, 718 microg/100 mg THp), indicating that the presence of repeating
N-acetyllactosamine units incorporated into the N-glycan moiety of THp is
donor specific. Furthermore, a higher expression of the Sd(a) determinant
on antennae which display N-acetyllactosamine elongation was observed,
suggesting a better accessibility for the
beta-N-acetylgalactosaminyltransferase. In order to characterize the
N-glycans containing repeating N- acetyllactosamine units, carbohydrate
chains were enzymatically released from THp and isolated. The
tetraantennary fraction, which accounts for more than 33% of the total
carbohydrate moiety of THp, was used to isolate oligosaccharides containing
additional N - acetyllactosamine units. Five N-linked tetraantennary
oligosaccharides containing a repeating N-acetyllactosamine unit were
identified, varying from structures bearing four Sd(a) determinants to
structures containing no Sd(a) determinant (see below). One compound was
used in order to specify the branch location of the additional N-
acetyllactosamine unit, and it appeared that only the Gal-6' and Gal-8'
residues were occupied by a repeating N -acetyllactosamine unit.
相似文献
39.
The demonstration that interleukin 2 (IL-2) is a lectin specific for
oligomannosides allows to understand a new function for this cytokine: as a
bifunctional molecule when bound to its receptor ss, IL-2 associates the
latter which the CD3/TCR complex, interacting with oligosaccharides of CD3
through its carbohydrate-recognition domain (Zanetta et al. , 1996,
Biochem. J., 318, 49-53). This induces the tyrosine phosphorylation of the
IL-2R beta by ++p56(lck) , the first step of the IL-2-dependent signaling.
Since this specific association is disrupted in vitro by oligomannosides
with five and six mannose residues, we made the hypothesis that pathogenic
cells or microorganisms could bind IL-2, consequently disturbing the IL-2-
dependent response. This study shows that the pathogenic yeast Candida
albicans (in contrast with nonpathogenic yeasts) binds high amounts of IL-2
as did cancer cells. In contrast with cancer cells, yeasts do not bind the
Man6GlcNAc2-specific lectin CSL, an endogenous "amplifier of activation
signals" (Zanetta et al. , 1995, Biochem. J., 311, 629-636).
相似文献
40.