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排序方式: 共有249条查询结果,搜索用时 15 毫秒
91.
92.
Il1rn−/− mice spontaneously develop arthritis and aortitis by
an autoimmune mechanism and also develop dermatitis by an autoinflammatory mechanism.
Here, we show that Rag2−/−Il1rn−/−
mice develop spontaneous colitis with high mortality, making a contrast to the suppression
of arthritis in these mice. Enhanced IL-17A expression in group 3 innate lymphoid cells
(ILC3s) was observed in the colon of
Rag2−/−Il1rn−/− mice.
IL-17A-deficiency prolonged the survival of
Rag2−/−Il1rn−/− mice, suggesting
a pathogenic role of this cytokine in the development of intestinal inflammation. Although
IL-17A-producing T cells were increased in Il1rn−/− mice,
these mice did not develop colitis, because CD4+Foxp3+ regulatory T
cell population was also expanded. Thus, excess IL-1 signaling and IL-1-induced IL-17A
from ILC3s cause colitis in Rag2−/−Il1rn−/− mice in
which Treg cells are absent. These observations suggest that the balance between
IL-17A-producing cells and Treg cells is important to keep the immune homeostasis of the
colon. 相似文献
93.
Hiro Takahashi Kimie Sai Yoshiro Saito Nahoko Kaniwa Yasuhiro Matsumura Tetsuya Hamaguchi Yasuhiro Shimada Atsushi Ohtsu Takayuki Yoshino Toshihiko Doi Haruhiro Okuda Risa Ichinohe Anna Takahashi Ayano Doi Yoko Odaka Misuzu Okuyama Nagahiro Saijo Jun-ichi Sawada Hiromi Sakamoto Teruhiko Yoshida 《PloS one》2014,9(8)
Interindividual variation in a drug response among patients is known to cause serious problems in medicine. Genomic information has been proposed as the basis for “personalized” health care. The genome-wide association study (GWAS) is a powerful technique for examining single nucleotide polymorphisms (SNPs) and their relationship with drug response variation; however, when using only GWAS, it often happens that no useful SNPs are identified due to multiple testing problems. Therefore, in a previous study, we proposed a combined method consisting of a knowledge-based algorithm, 2 stages of screening, and a permutation test for identifying SNPs. In the present study, we applied this method to a pharmacogenomics study where 109,365 SNPs were genotyped using Illumina Human-1 BeadChip in 168 cancer patients treated with irinotecan chemotherapy. We identified the SNP rs9351963 in potassium voltage-gated channel subfamily KQT member 5 (KCNQ5) as a candidate factor related to incidence of irinotecan-induced diarrhea. The p value for rs9351963 was 3.31×10−5 in Fisher''s exact test and 0.0289 in the permutation test (when multiple testing problems were corrected). Additionally, rs9351963 was clearly superior to the clinical parameters and the model involving rs9351963 showed sensitivity of 77.8% and specificity of 57.6% in the evaluation by means of logistic regression. Recent studies showed that KCNQ4 and KCNQ5 genes encode members of the M channel expressed in gastrointestinal smooth muscle and suggested that these genes are associated with irritable bowel syndrome and similar peristalsis diseases. These results suggest that rs9351963 in KCNQ5 is a possible predictive factor of incidence of diarrhea in cancer patients treated with irinotecan chemotherapy and for selecting chemotherapy regimens, such as irinotecan alone or a combination of irinotecan with a KCNQ5 opener. Nonetheless, clinical importance of rs9351963 should be further elucidated. 相似文献
94.
95.
Ami Y Nagata N Shirato K Watanabe R Iwata N Nakagaki K Fukushi S Saijo M Morikawa S Taguchi F 《Microbiology and immunology》2008,52(2):118-127
SARS-CoV grows in a variety of tissues that express its receptor, although the mechanism for high replication in the lungs and severe respiratory illness is not well understood. We recently showed that elastase enhances SARS-CoV infection in cultured cells, which suggests that SARS development may be due to elastase-mediated, enhanced SARS-CoV infection in the lungs. To explore this possibility, we examined whether co-infection of mice with SARS-CoV and Pp, a low-pathogenic bacterium which elicits elastase production in the lungs, induces exacerbation of pneumonia. Mice co-infected with SARS-CoV and Pp developed severe respiratory disease with extensive weight loss, resulting in a 33~90% mortality rate. Mice with exacerbated pneumonia showed enhanced virus infection in the lungs and histopathological lesions similar to those found in human SARS cases. Intranasal administration of LPS, another elastase inducer, showed an effect similar to that of Pp infection. Thus, this study shows that exacerbated pneumonia in mice results from co-infection with SARS-CoV and a respiratory bacterium that induces elastase production in the lungs, suggesting a possible role for elastase in the exacerbation of pneumonia. 相似文献
96.
Nakamura K Miyazato A Koguchi Y Adachi Y Ohno N Saijo S Iwakura Y Takeda K Akira S Fujita J Ishii K Kaku M Kawakami K 《Microbes and infection / Institut Pasteur》2008,10(10-11):1223-1227
The present study was designed to elucidate the role of TLR2, TLR4 and dectin-1 in the production of IL-12p40 by bone marrow-derived dendritic cells (BM-DCs) infected with Penicillium marneffei. IL-12p40 production was almost completely abrogated in BM-DCs from TLR2 gene-knockout (KO) and MyD88KO mice, but not from TLR4-defective C3H/HeJ mice compared to those from control mice. Furthermore, BM-DCs from dectin-1KO mice faintly produced IL-12p40 upon stimulation with this fungus. Using a luciferase reporter assay, P. marneffei activated NF-kappaB in HEK293 cells transfected with the TLR2 gene, but not with the dectin-1 gene, and their co-transfection did not lead to further increase in this response. These results indicate that TLR2 and dectin-1 are essential in sensing P. marneffei for the activation of BM-DCs. 相似文献
97.
S Saijo M Kotani K Habu C Ishitsuka H Yamamoto T Sekiguchi Y Iwakura 《Journal of immunology (Baltimore, Md. : 1950)》1999,163(10):5700-5707
Previously, we reported that human T cell leukemia virus type I env-pX region-introduced transgenic (pX-Tg) mice developed an inflammatory polyarthropathy associated with a development of autoimmunity. To elucidate roles of autoimmunity in the development of arthritis, the immune cells were reciprocally replaced between pX-Tg mice and non-transgenic (Tg) mice. When bone marrow (BM) cells and spleen cells from pX-Tg mice were transferred into irradiated non-Tg mice, arthritis developed in these mice. In contrast, arthritis in pX-Tg mice was completely suppressed by non-Tg BM and spleen cells. Similar results were obtained with BM cells only. After the transplantation, T cells, B cells, and macrophages were replaced completely, whereas cells in the joints were replaced partially. In those mice, serum Ig and rheumatoid factor levels correlated with the disease development, and inflammatory cytokine expression was elevated in the arthritic joints. Furthermore, involvement of T cells in the joint lesion was suggested, because the incidence was greatly reduced in athymic nu/nu mice although small proportion of the mice still developed arthritis. These observations suggest that BM stem cells are abnormal, causing autoimmunity in pX-Tg mice, and this autoimmunity plays an important, but not absolute, role in the development of arthritis in this Tg mouse. 相似文献
98.
Horiuchi K Tsurushima H Soo Kim B Qin Liu S Saijo K Saijo Y Nukiwa T Nomura N Matsumura M Ohno T 《Cytotechnology》1998,26(2):119-124
Human tumor specific cytotoxic T lymphocytes (CTL) were expanded on formalin-fixed autologous target tumor cells derived from
glioblastoma multiforme. Growth response of the CTL restimulated with the fixed target cells was larger than those with live
target cells. The results suggest that formalin-fixed tumor cells will be stable sources of tumor antigen for efficient autologous
CTL expansion and be useful for adoptive immunotherapy of tumors.
This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献
99.
Serotonin Synthesis Rate Measured in Living Dog Brain by Positron Emission Tomography 总被引:8,自引:1,他引:7
M. Diksic S. Nagahiro T. Chaly T. L. Sourkes† Y. L. Yamamoto W. Feindel 《Journal of neurochemistry》1991,56(1):153-162
In vivo measurements by positron emission tomography of the brain serotonin synthesis rates in the normal dog, in the dog with increased plasma tryptophan concentration, and in the dog under different arterial oxygen tensions are described. The method described here permits repeated measurements in the same brain for the first time. An increase in the plasma tryptophan concentration from 16.6 to 191.5 and then to 381 microM resulted in close to a linear increase in the brain serotonin synthesis rate. When PaO2 was raised from 76 +/- 2 to 106 +/- 1 mm Hg, the rate of serotonin synthesis in the dog brain increased from 39 +/- 8 to 54 +/- 10 pmol g-1 min-1. The estimates of the Michaelis-Menten constants, Kappm and Vmax, for the transport of tryptophan through the blood-brain barrier are 303 +/- 54 microM and 63 +/- 10 nmol g-1 min-1, respectively. 相似文献
100.
Y. Ashida T. Saijo H. Kuriki H. Makino S. Terao Y. Maki 《Prostaglandins & other lipid mediators》1983,26(6):955-972
AA-861, a selective 5-lipoxygenase inhibitor, suppressed A23187-induced formations of 5-HETE and LTB4 in rat peritoneal macrophages. Immunologically-stimulated generation of SRS-A was also inhibited in guinea pig lung and rat peritoneal cavity. AA-861 had no effects on histamine release from rat mast cels or passive cutaneous anaphylaxis in rats. Essentially no antagonistic activity to LDT4 or histamine was observed. This compound exerted an obvious inhibition of allergic bronchoconstriction in guinea pigs and a moderate reduction of carrageenin-induced paw edema and pleurisy in rats. These findins suggest that SRS-A plays an important role in asthmatic and inflammatory reactions. 相似文献