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Kim AT Verheijden Linette EM Willemsen Saskia Braber Thea Leusink-Muis Dianne JM Delsing Johan Garssen Aletta D Kraneveld Gert Folkerts 《Respiratory research》2015,16(1)
Background
Allergic asthma is strongly associated with the exposure to house dust mite (HDM) and is characterized by eosinophilic pulmonary inflammation and airway hyperresponsiveness (AHR). Recently, there is an increased interest in using dietary oligosaccharides, also known as prebiotics, as a novel strategy to prevent the development of, or reduce, symptoms of allergy.Aim
We investigated the preventive capacity of dietary galacto-oligosaccharides (GOS) compared to an intra-airway therapeutic treatment with budesonide on the development of HDM-induced allergic asthma in mice.Methods
BALB/c mice were intranasally sensitized with 1 μg HDM on day 0 followed by daily intranasal challenge with PBS or 10 μg HDM on days 7 to 11. Two weeks prior to the first sensitization and throughout the experiment mice were fed a control diet or a diet containing 1% GOS. Reference mice were oropharyngeally instilled with budesonide (500 μg/kg) on days 7, 9, 11, and 13, while being fed the control diet. On day 14, AHR was measured by nebulizing increasing doses of methacholine into the airways. At the end of the experiment, bronchoalveolar lavage fluid (BALF) and lungs were collected.Results
Sensitization and challenge with HDM resulted in AHR. In contrast to budesonide, dietary intervention with 1% GOS prevented the development of AHR. HDM sensitization and challenge resulted in a significant increase in BALF leukocytes numbers, which was suppressed by budesonide treatment and dietary intervention with 1% GOS. Moreover, HDM sensitization and challenge resulted in significantly enhanced concentrations of IL-6, CCL17, IL-33, CCL5 and IL-13 in lung tissue. Both dietary intervention with 1% GOS or budesonide treatment significantly decreased the HDM-induced increased concentrations of CCL5 and IL-13 in lung tissue, while budesonide also reduced the HDM-enhanced concentrations of IL-6 and CCL17 in lung tissue.Conclusion
Not only did dietary intervention with 1% GOS during sensitization and challenge prevent the induction of airway eosinophilia and Th2-related cytokine and chemokine concentrations in the lung equally effective as budesonide treatment, it also prevented AHR development in HDM-allergic mice. GOS might be useful for the prevention and/or treatment of symptoms in asthmatic disease.Electronic supplementary material
The online version of this article (doi:10.1186/s12931-015-0171-0) contains supplementary material, which is available to authorized users. 相似文献45.
Diahann TSL Jansen Hanane el Bannoudi Ramon Arens Kim LL Habets Marjolijn Hameetman Tom WJ Huizinga Jeroen N. Stoop René EM Toes 《Arthritis research & therapy》2015,17(1)
IntroductionAbatacept is a fusion protein of human cytotoxic T-lymphocyte–associated protein (CTLA)-4 and the Fc portion of human immunoglobulin G1 (IgG1). It is believed to be effective in the treatment of rheumatoid arthritis by inhibiting costimulation of T cells via blocking CD28–B7 interactions as CTLA-4 binds to both B7.1 (CD80) and B7.2 (CD86). However, the interaction of CD28 with B7 molecules is crucial for activation of naive cells, whereas it is unclear whether the action of already activated CD4+ T cells, which are readily present in established disease, also depends on this interaction. The aim of this study was to determine whether the mode of action of abatacept depends solely on its ability to halt T cell activation in established disease.MethodsArthritis was induced in thymectomized male DBA/1 mice by immunisation with bovine collagen type II. The mice were subsequently depleted for CD4+ T cells. Abatacept or control treatment was started when 80 % of the mice showed signs of arthritis. Arthritis severity was monitored by clinical scoring of the paws, and anti-collagen antibody levels over time were determined by enzyme-linked immunosorbent assay.ResultsTreatment with abatacept in the absence of CD4+ T cells resulted in lower disease activity. This was associated with decreasing levels of collagen-specific IgG1 and IgG2a antibodies, whereas the antibody levels in control or CD4+ T cell–depleted mice increased over time.ConclusionsThese results show that abatacept decreased disease activity in the absence of CD4+ T cells, indicating that the mode of action of abatacept in established arthritis does not depend entirely on its effects on CD4+ T cell activation. 相似文献
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Irene EM Bultink D?rte Hamann Marc A Seelen Margreet H Hart Ben AC Dijkmans Mohamed R Daha Alexandre E Voskuyl 《Arthritis research & therapy》2007,8(6):R183
Infection imposes a serious burden on patients with systemic lupus erythematosus (SLE). The increased infection rate in SLE
patients has been attributed in part to defects of immune defence. Recently, the lectin pathway of complement activation has
also been suggested to play a role in the occurrence of infections in SLE. In previous studies, SLE patients homozygous for
mannose-binding lectin (MBL) variant alleles were at an increased risk of acquiring serious infections in comparison with
patients who were heterozygous or homozygous for the normal allele. This association suggests a correlation between functional
MBL level and occurrence of infections in SLE patients. We therefore investigated the biological activity of MBL and its relationship
with the occurrence of infections in patients with SLE. Demographic and clinical data were collected in 103 patients with
SLE. Functional MBL serum levels and MBL-induced C4 deposition were measured by enzyme-linked immunosorbent assay using mannan
as coat and an MBL- or C4b-specific monoclonal antibody. The complete MBL-dependent pathway activity was determined by using
an assay that measures the complete MBL pathway activity in serum, starting with binding of MBL to mannan, and was detected
with a specific monoclonal antibody against C5b-9. Charts were systematically reviewed to obtain information on documented
infections since diagnosis of SLE. Major infections were defined as infections requiring hospital admission and intravenous
administration of antibiotics. In total, 115 infections since diagnosis of lupus, including 42 major infections, were documented
in the 103 SLE patients (mean age 41 ± 13 years, mean disease duration 7 ± 4 years). The percentage of SLE patients with severe
MBL deficiency was similar to that in 100 healthy controls: 13% versus 14%, respectively. Although deposition of C4 to mannan
and MBL pathway activity were reduced in 21% and 43% of 103 SLE patients, respectively, neither functional MBL serum levels
nor MBL pathway activity was associated with infections or major infections in regression analyses. In conclusion, SLE patients
frequently suffer from infections, but deficiency of functional MBL does not confer additional risk. 相似文献
47.
I. Voiculescu Elke Back Alessandra M. V. Duncan H. Schwaibold W. Schempp 《Human genetics》1987,76(3):298-301
Summary A case of complete trisomy 22 in live-born female child with multiple malformations is reported. The karyotype of the index patient had 46 chromosomes, with one chromosome 22 missing and one supranumerary metacentric chromosome. Different banding methods and in situ hybridization revealed that the extra chromosome consists of the long arms and a part of the short arms of two chromosomes 22. Our report supplies further proof that a fetus with complete trisomy 22 can occasionally survive to term, but the condition is not compatible with life over a long period. 相似文献
48.
Phylogenetic analysis of the outer-membrane-protein genes of Chlamydiae, and its implication for vaccine development 总被引:9,自引:0,他引:9
Examination of 18 complete and 6 partial sequences of the major outer-
membrane protein from 24 chlamydiae isolates was used to reconstruct their
evolutionary relationships. From this analysis, assuming that the clades
with 100% bootstrap support are correct, come the following conclusions:
(1) The tree of these sequences is not congruent with the phylogeny of the
hosts, and thus host switching would seem to have occurred, thereby
limiting the extent to which there has been coevolution of parasite and
host. (2) The tree is also noncongruent with clustering by type of cell
infected, thereby limiting the extent to which there has been coevolution
of parasite and the cell type that it infects. (3) The tree is also
noncongruent with clustering by the organ infected (eyes or genitalia),
thereby limiting the extent to which there has been coevolution of parasite
and the organ that it infects. (4) The tree is also noncongruent with
genital strains arising from lymphogranuloma venereum strains. (5) The tree
is also noncongruent with the geographic site at which the isolates were
obtained, thereby limiting the extent of divergence explained by geographic
separation. (6) There are estimated to be 185 amino acid positions that are
invariable (as opposed to unvaried) in the major outer-membrane protein.
There are 10 unvaried positions in the variable domains, of which 9 appear
to be invariable, giving some reason to hope that development of a vaccine
might be possible. (7) The rate of change of this protein is too small to
see increased divergence over the time span of isolation of these genes,
giving hope to any vaccine having longevity. Bootstrapping supports those
portions of the tree on which the first five conclusions above depend. The
picture that these results provide is more one of pathogen versatility than
one of coevolutionary constraints. In addition, we examined 10 60-KDa,
outer-membrane protein- 2 genes, all but one of which were from these same
strains. The tree was not, among the trachomatis strains, congruent with
the major-outer- membrane protein tree, suggesting that gene exchange could
be occurring among strains. Moreover, there is an apparent slowdown in
divergence in this gene, among the trachomatis strains.
相似文献
49.
Angelika Wientzek María‐José Tormo Díaz Jose Maria Huerta Castaño Pilar Amiano Larraitz Arriola Kim Overvad Jane Nautrup Østergaard Marie‐Aline Charles Guy Fagherazzi Domenico Palli Benedetta Bendinelli Guri Skeie Kristin Benjaminsen Borch Wanda Wendel‐Vos Ellen de Hollander Anne M. May Marjolein EM den Ouden Antonia Trichopoulou Elissavet Valanou Stefan Söderberg Paul W. Franks Soren Brage Matthäus Vigl Heiner Boeing Ulf Ekelund 《Obesity (Silver Spring, Md.)》2014,22(5):E127-E134
50.