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61.
Several social and reproductive behaviors are under the influence of the vomeronasal (VN) organ; VN neurons detect odorous molecules emitted by individuals of the same species. There are two types of VN neurons, and these differ in their expression of chemosensory receptors and G protein subunits. The significance of this dichotomy is largely unknown. VN neurons express high levels of either G alpha i2 or G alpha o. A mouse line carrying a targeted disruption of the G alpha i2 gene offered the opportunity for studying the effects of a lack of receptor signaling through the heterotrimeric Gi2 protein in one VN cell type. As a consequence of this deficiency, the number of VN neurons that normally express G alpha i2 is decreased by half. These residual neurons are defective in eliciting a response in their target neurons in the accessory olfactory bulb. Moreover, G alpha i2 mutant mice show alterations in behaviors for which an intact VN organ is known to be important. Display of maternal aggressive behavior is severely blunted, and male mice show significantly less aggression toward an intruder. However, male mice show unaltered sexual-partner preference. This suggests that the two types of VN neurons may have separate functions in mediating behavioral changes in response to chemosensory information. 相似文献
62.
63.
Börjesson A Norlin A Wang X Andersson R Folkesson HG 《American journal of physiology. Lung cellular and molecular physiology》2000,278(1):L3-12
Intestinal ischemia-reperfusion commonly occurs in critically ill patients and may lead to the development of remote organ injury, frequently involving the lungs. In the present study, alveolar liquid clearance was studied in ventilated, anesthetized rats subjected to 45 min of intestinal ischemia followed by 3 h of reperfusion. An isosmolar 5% albumin solution was instilled into the lungs, and alveolar liquid clearance was measured from the increase in alveolar protein concentration as water was reabsorbed over 45 min. Intestinal ischemia-reperfusion resulted in a 76% increase in alveolar liquid clearance compared with the control value (P < 0.05). The stimulated alveolar liquid clearance seen after intestinal ischemia-reperfusion was not inhibited by propranolol, indicating stimulation through a noncatecholamine-dependent pathway. Intestinal ischemia-reperfusion did not result in increased intracellular cAMP levels. Amiloride inhibited similar fractions in animals subjected to ischemia-reperfusion and control animals. Administration of a neutralizing polyclonal anti-tumor necrosis factor-alpha antibody before induction of intestinal ischemia completely inhibited the increased alveolar liquid clearance observed after intestinal ischemia-reperfusion. In conclusion, our results suggest that intestinal ischemia-reperfusion in rats leads to stimulation of alveolar liquid clearance and that this stimulation is mediated, at least in part, by a tumor necrosis factor-alpha-dependent mechanism. 相似文献
64.
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65.
66.
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
67.
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
68.
69.
EM Armstrong 《BMJ (Clinical research ed.)》1996,312(7042):1320.2
70.
Structure and regulation of the anthranilate synthase genes in Pseudomonas aeruginosa: II. Cloning and expression in Escherichia coli 总被引:7,自引:0,他引:7
Crawford IP; Wilde A; Yelverton EM; Figurski D; Hedges RW 《Molecular biology and evolution》1986,3(5):449-458
The genes for the large and small subunits of anthranilate synthase (trpE
and trpG, respectively) have been cloned from Pseudomonas aeruginosa PAC174
into E. coli by R-prime formation with the broad-host- range plasmid
R68.44. Sequential subcloning into plasmid vectors reduced the active
Pseudomonas DNA fragment to a length of 3.1 kb. We obtained evidence that
this region contains the promoter for its own expression and retains a
vestigial regulatory response to tryptophan scarcity or excess.
相似文献