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951.
Kazuyasu Chihara Yukihiro Kimura Chisato Honjoh Shota Yamauchi Kenji Takeuchi Kiyonao Sada 《Experimental cell research》2014
Adaptor protein c-Abl SH3 domain-binding protein-2 (3BP2) is known to play regulatory roles in immunoreceptor-mediated signal transduction. We have previously demonstrated that Tyr174, Tyr183 and Tyr446 in mouse 3BP2 are predominantly phosphorylated by Syk, and the phosphorylation of Tyr183 and the Src homology 2 (SH2) domain of mouse 3BP2 are critical for B cell receptor (BCR)-induced activation of nuclear factor of activated T cells (NFAT) in human B cells. In this report, we have shown that Syk, but not Abl family protein-tyrosine kinases, is critical for BCR-mediated tyrosine phosphorylation of 3BP2 in chicken DT40 cells. Mutational analysis showed that Tyr174, Tyr183 and Tyr426 of chicken 3BP2 are the major phosphorylation sites by Syk and the SH2 domain of 3BP2 is critical for tyrosine phosphorylation. In addition, phosphorylation of Tyr426 is required for the inducible interaction with the SH2 domain of Vav3. Moreover, the expression of the mutant form of 3BP2 in which Tyr426 was substituted to Phe resulted in the reduction in BCR-mediated Rac1 activation, when compared with the case of wild-type. Altogether, these data suggest that 3BP2 is involved in the activation of Rac1 through the regulation of Vav3 by Syk-dependent phosphorylation of Tyr426 following BCR stimulation. 相似文献
952.
Shingo Noguchi Kazuhiro Yatera Ke-Yong Wang Keishi Oda Kentarou Akata Kei Yamasaki Toshinori Kawanami Hiroshi Ishimoto Yumiko Toyohira Hiroaki Shimokawa Nobuyuki Yanagihara Masato Tsutsui Hiroshi Mukae 《Respiratory research》2014,15(1):92
Background
Increased expression of nitric oxide synthase (NOS) and an increase in plasma nitrite plus nitrate (NOx) have been reported in patients with pulmonary fibrosis, suggesting that nitric oxide (NO) plays an important role in its development. However, the roles of the entire NO and NOS system in the pathogenesis of pulmonary fibrosis still remain to be fully elucidated. The aim of the present study is to clarify the roles of NO and the NOS system in pulmonary fibrosis by using the mice lacking all three NOS isoforms.Methods
Wild-type, single NOS knockout and triple NOS knockout (n/i/eNOS−/−) mice were administered bleomycin (BLM) intraperitoneally at a dose of 8.0 mg/kg/day for 10 consecutive days. Two weeks after the end of the procedure, the fibrotic and inflammatory changes of the lung were evaluated. In addition, we evaluated the effects of long-term treatment with isosorbide dinitrate, a NO donor, on the n/i/eNOS−/− mice with BLM-induced pulmonary fibrosis.Results
The histopathological findings, collagen content and the total cell number in bronchoalveolar lavage fluid were the most severe/highest in the n/i/eNOS−/− mice. Long-term treatment with the supplemental NO donor in n/i/eNOS−/− mice significantly prevented the progression of the histopathological findings and the increase of the collagen content in the lungs.Conclusions
These results provide the first direct evidence that a lack of all three NOS isoforms led to a deterioration of pulmonary fibrosis in a BLM-treated murine model. We speculate that the entire endogenous NO and NOS system plays an important protective role in the pathogenesis of pulmonary fibrosis. 相似文献953.
Ariyasu T Tanaka T Fujioka N Yanai Y Yamamoto S Yamauchi H Ikegami H Ikeda M Kurimoto M 《In vitro cellular & developmental biology. Animal》2005,41(1-2):50-56
Summary Interferon-alpha (IFN-α) has recently been shown to modulate in vitro T helper (Th) 1-driven responses in the peripheral blood
mononuclear cells (PBMC) of patients with hepatitis B virus or C virus infection. In this study, we examined the in vitro
effects of IFN-α subtypes (IFN-α1, −α2, −α5, −α8, and −α10) on the Th1/Th2 balance in PBMC obtained from patients with hepatitis
virus infection-associated liver disorders and chronic hepatitis (CH), in comparison with the effect on healthy control volunteer
PBMC. The Th1-type cell percentages and Th1/Th2 ratios were significantly higher in the PBMC of patients when compared with
controls both before and after cultivation in vitro, with the IFN-α subtypes. The IFNα-5 induced an increase in the Th2-type
cell percentages in both control and patient PBMC, resulting in that IFN-α5 lowered the Th1/Th2 ratio in patients with CH.
Furthermore, statistical analysis revealed that IFN-α8 significantly promoted an increase in the Th1/Th2 ratios of PBMC from
patients with CH and liver cirrhosis (LC) but not that of PBMC from patients with LC-hepatocellular carcinoma (HCC) and HCC.
These findings imply that hepatitis virus infection and its disease status modify the effects of IFN-α subtypes on Th1 and
Th2 immune balance in patients. Our findings should help to elucidate the mechanisms underlying successful IFN therapy for
hepatitis virus infection and prevention of hepatocellular carcinogenesis. 相似文献
954.
Sequence of membrane-associated thyroid hormone binding protein from bovine liver: its identity with protein disulphide isomerase 总被引:7,自引:0,他引:7
K Yamauchi T Yamamoto H Hayashi S Koya H Takikawa K Toyoshima R Horiuchi 《Biochemical and biophysical research communications》1987,146(3):1485-1492
The complementary DNAs of the bovine liver membrane-associated 3,5,3'-triiodo-L-thyronine binding protein with 55 k-dalton (T3BP) were cloned and the nucleotide sequences were determined. Monospecific antibodies against T3BP were used to screen a bovine liver cDNA library in lambda gtll. We analyzed the sequences of two cloned T3BP cDNAs. The clones encoded a polypeptide of 510 amino acid residues, including a signal peptide of 20 amino acid. Northern blot analysis of bovine and human RNA showed that the mRNAs encoding T3BP are 2.7 kilobase in length. Amino acid sequence of N-terminal and other three peptides isolated from purified T3BP were found in the predicted amino acid sequence from the cDNA sequence. The predicted amino acid sequence is closely homologous (93%) with that of rat protein disulphide isomerase (EC 5.3.4.1), which catalyzes the isomerization of the protein disulphide bonds and has been shown to play an important role in post-translational regulation. The results suggest that T3BP and protein disulphide isomerase should be the same protein. 相似文献
955.
956.
Uchida-Kitajima S Yamauchi T Takashina Y Okada-Iwabu M Iwabu M Ueki K Kadowaki T 《FEBS letters》2008,582(20):3037-3044
Knowledge of the regulatory factors associated with down-regulation of adiponectin gene expression and up-regulation of PAI-1 gene expression is crucial to understand the pathophysiological basis of obesity and metabolic diseases, and could establish new treatment strategies for these conditions. We showed that expression of 5-HT(2A) receptors was up-regulated in hypertrophic 3T3-L1 adipocytes, which exhibited decreased expression of adiponectin and increased expression of PAI-1. 5-HT(2A) receptor antagonists and suppression of 5-HT(2A) receptor gene expression enhanced adiponectin expression. Activation of Gq negatively regulated adiponectin expression, and inhibition of mitogen-activated protein kinase reversed the Gq-induced effect. Moreover, the 5-HT(2A) receptor blockade reduced PAI-1 expression. These findings indicate that antagonism of 5-HT(2A) receptors in adipocytes could improve the obesity-linked decreases in adiponectin expression and increases in PAI-1 expression. 相似文献
957.
To explore the interactions between the host, environment and bacterium responsible for the different manifestations of Helicobacter pylori infection, we examined the effect of acidic conditions on H. pylori-induced interleukin (IL)-8 expression. AGS gastric epithelial cells were exposed to acidic pH and infected with H. pylori[wild-type strain, its isogenic cag pathogenicity island (PAI) mutant or its oipA mutant]. Exposure of AGS cells to acidic pH alone did not enhance IL-8 production. However, following exposure to acidic conditions, H. pylori infection resulted in marked enhancement of IL-8 production which was independent of the presence of the cag PAI and OipA, indicating that H. pylori and acidic conditions act synergistically to induce gastric mucosal IL-8 production. In neutral pH environments H. pylori-induced IL-8 induction involved the NF-kappaB pathways, the extracellular signal-regulated kinase (ERK)-->c-Fos/c-Jun-->activating protein (AP-1) pathways, JNK-->c-Jun-->AP-1 pathways and the p38 pathways. At acidic pH H. pylori-induced augmentation of IL-8 production involved markedly upregulated the NF-kappaB pathways and the ERK-->c-Fos-->AP-1 pathways. In contrast, activation of the JNK-->c-Jun-->AP-1 pathways and p38 pathways were pH independent. These results might explain the clinical studies in which patients with duodenal ulcers had higher levels of IL-8 in the antral gastric mucosa than patients with simple H. pylori gastritis. 相似文献
958.
959.
960.
Hiroshi Nakano Yoko Shibata Sumito Inoue Akira Igarashi Keiko Yamauchi Shuichi Abe Masamichi Sato Yasuko Aida Keiko Nunomiya Tomomi Kimura Takako Nemoto Tetsu Watanabe Tsuneo Konta Yoshiyuki Ueno Takeo Kato Takamasa Kayama Isao Kubota 《PloS one》2013,8(12)