全文获取类型
收费全文 | 1554篇 |
免费 | 100篇 |
出版年
2023年 | 8篇 |
2021年 | 16篇 |
2020年 | 7篇 |
2019年 | 16篇 |
2018年 | 15篇 |
2017年 | 13篇 |
2016年 | 27篇 |
2015年 | 43篇 |
2014年 | 56篇 |
2013年 | 83篇 |
2012年 | 74篇 |
2011年 | 76篇 |
2010年 | 57篇 |
2009年 | 44篇 |
2008年 | 83篇 |
2007年 | 80篇 |
2006年 | 84篇 |
2005年 | 74篇 |
2004年 | 60篇 |
2003年 | 78篇 |
2002年 | 55篇 |
2001年 | 55篇 |
2000年 | 55篇 |
1999年 | 50篇 |
1998年 | 16篇 |
1997年 | 19篇 |
1996年 | 15篇 |
1995年 | 14篇 |
1994年 | 10篇 |
1993年 | 15篇 |
1992年 | 38篇 |
1991年 | 46篇 |
1990年 | 26篇 |
1989年 | 28篇 |
1988年 | 22篇 |
1987年 | 22篇 |
1986年 | 25篇 |
1985年 | 19篇 |
1984年 | 17篇 |
1983年 | 19篇 |
1982年 | 9篇 |
1981年 | 9篇 |
1979年 | 5篇 |
1977年 | 12篇 |
1976年 | 5篇 |
1975年 | 10篇 |
1974年 | 9篇 |
1973年 | 5篇 |
1968年 | 5篇 |
1966年 | 4篇 |
排序方式: 共有1654条查询结果,搜索用时 15 毫秒
991.
Hiroaki Shibahara Michiyo Higashi Chihaya Koriyama Seiya Yokoyama Iwao Kitazono Yasuhiro Kurumiya Michihiko Narita Shingo Kuze Takanori Kyokane Saburo Mita Toshiyuki Arai Takehito Kato Norihiro Yuasa Ryuzo Yamaguchi Hitoshi Kubota Hideaki Suzuki Satoshi Baba Karine Rousseau Surinder K. Batra Suguru Yonezawa 《PloS one》2014,9(4)
Mucins have been associated with survival in various cancer patients, but there have been no studies of mucins in small bowel carcinoma (SBC). In this study, we investigated the relationships between mucin expression and clinicopathologic factors in 60 SBC cases, in which expression profiles of MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC6 and MUC16 in cancer and normal tissues were examined by immunohistochemistry. MUC1, MUC5AC and MUC16 expression was increased in SBC lesions compared to the normal epithelium, and expression of these mucins was related to clinicopathologic factors, as follows: MUC1 [tumor location (p = 0.019), depth (p = 0.017) and curability (p = 0.007)], MUC5AC [tumor location (p = 0.063) and lymph node metastasis (p = 0.059)], and MUC16 [venous invasion (p = 0.016) and curability (p = 0.016)]. Analysis of 58 cases with survival data revealed five factors associated with a poor prognosis: poorly-differentiated or neuroendocrine histological type (p<0.001), lymph node metastasis (p<0.001), lymphatic invasion (p = 0.026), venous invasion (p<0.001) and curative resection (p<0.001), in addition to expression of MUC1 (p = 0.042), MUC5AC (p = 0.007) and MUC16 (p<0.001). In subsequent multivariate analysis with curability as the covariate, lymph node metastasis, venous invasion, and MUC5AC and/or MUC16 expression were significantly related to the prognosis. Multivariate analysis in curative cases (n = 45) showed that SBC with MUC5AC and/or MUC16 expression had a significantly independent high hazard risk after adjusting for the effects of venous invasion (hazard ratio: 5.6, 95% confidence interval: 1.8–17). In conclusion, the study shows that a MUC5AC-positive and/or MUC16-positive status is useful as a predictor of a poor outcome in patients with SBC. 相似文献
992.
Kyoko Oh-oka Hiroshi Kono Kayoko Ishimaru Kunio Miyake Takeo Kubota Hideoki Ogawa Ko Okumura Shigenobu Shibata Atsuhito Nakao 《PloS one》2014,9(5)
Background & Aims
The circadian clock drives daily rhythms in behavior and physiology. A recent study suggests that intestinal permeability is also under control of the circadian clock. However, the precise mechanisms remain largely unknown. Because intestinal permeability depends on tight junction (TJ) that regulates the epithelial paracellular pathway, this study investigated whether the circadian clock regulates the expression levels of TJ proteins in the intestine.Methods
The expression levels of TJ proteins in the large intestinal epithelium and colonic permeability were analyzed every 4, 6, or 12 hours between wild-type mice and mice with a mutation of a key clock gene Period2 (Per2; mPer2m/m). In addition, the susceptibility to dextran sodium sulfate (DSS)-induced colitis was compared between wild-type mice and mPer2m/m mice.Results
The mRNA and protein expression levels of Occludin and Claudin-1 exhibited daily variations in the colonic epithelium in wild-type mice, whereas they were constitutively high in mPer2m/m mice. Colonic permeability in wild-type mice exhibited daily variations, which was inversely associated with the expression levels of Occludin and Claudin-1 proteins, whereas it was constitutively low in mPer2m/m mice. mPer2m/m mice were more resistant to the colonic injury induced by DSS than wild-type mice.Conclusions
Occludin and Claudin-1 expressions in the large intestine are under the circadian control, which is associated with temporal regulation of colonic permeability and also susceptibility to colitis. 相似文献993.
994.
Kenji Tagai Maiko Ono Manabu Kubota Soichiro Kitamura Keisuke Takahata Chie Seki Yuhei Takado Hitoshi Shinotoh Yasunori Sano Yasuharu Yamamoto Kiwamu Matsuoka Hiroyuki Takuwa Masafumi Shimojo Manami Takahashi Kazunori Kawamura Tatsuya Kikuchi Maki Okada Haruhiko Akiyama Hitoshi Shimada 《Neuron》2021,109(1):42-58.e8
995.
996.
997.
998.
In the present study, we investigated the relationship between ornithine decarboxylase, MAP kinase, and MMP-2 expression in vitro. Overexpression of ornithine decarboxylase cDNA induced MMP-2 expression both at mRNA and protein levels. Promoter analysis and gel shift assay showed that p53 and Ets-1 were involved in MMP-2 expression in ornithine decarboxylase overexpressing transfectants. Erk and p38 MAP kinase were significantly activated. Using specific inhibitors of MEK and p38, we clarified that MMP-2 expression was induced via both Erk and p38 MAP kinase signaling pathways. This is the first report showing the existence of a causal relationship between ornithine decarboxylase expression, Erk and p38 MAP kinase activation, and MMP-2 expression. 相似文献
999.
Risk assessment of meat and milk from cloned animals 总被引:4,自引:0,他引:4
Research on, and commercialization of, cloned cattle has been conducted for more than 20 years. Early techniques relied on the physical splitting of embryos or using embryo cells for nuclear transfer to generate cloned animals. Milk and meat from these animals entered into the human food market with no evidence of problems. With the advent of nuclear transfer, which enables the direct transference and preservation of high-value meat- and milk-producing genotypes to offspring, concerns have been raised about whether the products from somatic cell nuclear transfer-produced animals are safe for human consumption. Studies on the biochemical properties of food products from cloned and noncloned animals have thus far not detected any differences. All data to date indicate no significant differences in the measured parameters between animals created by nuclear transfer and normally bred animals. Public acceptance of cloned animal products depends upon forthcoming US Food and Drug Administration approval along with convincing safety data. 相似文献
1000.
Kubota Y Kinoshita K Suetomi K Fujimori A Takahashi S 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(5):2923-2931
Remarkably, apoptosis was induced by exposing peritoneal resident macrophages (PRM) of C3H mice, but not other strains of mice, to ionizing radiation. The molecular mechanism of this strain-specific apoptosis in PRM was studied. The apoptosis elicited in C3H mouse PRM 4 h after exposure was effectively blocked by proteasome inhibitors. Irradiation-induced disruption of mitochondrial transmembrane potential and the release of cytochrome c into the cytosol were also suppressed by a proteasome inhibitor but not by a caspase inhibitor. To determine whether the apoptosis occurred due to a depletion of antiapoptotic proteins, Bcl-2 family proteins were examined. Irradiation markedly decreased the level of Mcl-1, but not Bcl-2, Bcl-X(L), Bax, A1, or cIAP1. Mcl-1's depletion was suppressed by a proteasome inhibitor but not by a caspase inhibitor. The amount of Mcl-1 was well correlated with the rate of apoptosis in C3H mouse PRM exposed to irradiation and not affected by irradiation in radioresistant B6 mouse PRM. Irradiation increased rather than decreased the Mcl-1 mRNA expression in C3H mouse PRM. On the other hand, Mcl-1 protein synthesis was markedly suppressed by irradiation. Global protein synthesis was also suppressed by irradiation in C3H mouse PRM but not in B6 mouse PRM. The down-regulation of Mcl-1 expression with Mcl-1-specific small interfering RNA or antisense oligonucleotide significantly induced apoptosis in both C3H and B6 mouse PRM without irradiation. It was concluded that the apoptosis elicited in C3H mouse PRM by ionizing radiation was attributable to the depletion of Mcl-1 through radiation-induced arrest of global protein synthesis. 相似文献