全文获取类型
收费全文 | 280篇 |
免费 | 13篇 |
专业分类
293篇 |
出版年
2022年 | 6篇 |
2021年 | 10篇 |
2020年 | 8篇 |
2019年 | 10篇 |
2018年 | 9篇 |
2017年 | 7篇 |
2016年 | 10篇 |
2015年 | 10篇 |
2014年 | 15篇 |
2013年 | 24篇 |
2012年 | 20篇 |
2011年 | 24篇 |
2010年 | 7篇 |
2009年 | 7篇 |
2008年 | 15篇 |
2007年 | 11篇 |
2006年 | 11篇 |
2005年 | 10篇 |
2004年 | 3篇 |
2003年 | 9篇 |
2002年 | 3篇 |
2001年 | 2篇 |
2000年 | 4篇 |
1999年 | 3篇 |
1997年 | 11篇 |
1996年 | 1篇 |
1995年 | 2篇 |
1994年 | 3篇 |
1993年 | 1篇 |
1992年 | 3篇 |
1990年 | 2篇 |
1989年 | 2篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1986年 | 3篇 |
1985年 | 1篇 |
1982年 | 3篇 |
1981年 | 1篇 |
1980年 | 3篇 |
1979年 | 4篇 |
1978年 | 1篇 |
1977年 | 3篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1970年 | 1篇 |
1968年 | 1篇 |
1967年 | 2篇 |
1966年 | 1篇 |
排序方式: 共有293条查询结果,搜索用时 15 毫秒
291.
Takumi Itoh Ryo Hatano Yoshiya Horimoto Taketo Yamada Dan Song Haruna Otsuka Yuki Shirakawa Shuji Mastuoka Noriaki Iwao Thomas M. Aune Nam H. Dang Yutaro Kaneko Ko Okumura Chikao Morimoto Kei Ohnuma 《Cell death & disease》2021,12(6)
Triple-negative breast cancer (TNBC) has a poor prognosis compared to other breast cancer subtypes. Although epidermal growth factor receptor (EGFR) is overexpressed in TNBC, clinical trials with EGFR inhibitors including tyrosine kinase inhibitors (EGFR-TKI) in TNBC have heretofore been unsuccessful. To develop effective EGFR-targeted therapy for TNBC, the precise mechanisms of EGFR-TKI resistance in TNBC need to be elucidated. In this study, to understand the molecular mechanisms involved in the differences in EGFR-TKI efficacy on TNBC between human and mouse, we focused on the effect of IL-26, which is absent in mice. In vitro analysis showed that IL-26 activated AKT and JNK signaling of bypass pathway of EGFR-TKI in both murine and human TNBC cells. We next investigated the mechanisms involved in IL-26-mediated EGFR-TKI resistance in TNBC. We identified EphA3 as a novel functional receptor for IL-26 in TNBC. IL-26 induced dephosphorylation and downmodulation of EphA3 in TNBC, which resulted in increased phosphorylation of AKT and JNK against EGFR-TKI-induced endoplasmic reticulum (ER) stress, leading to tumor growth. Meanwhile, the blockade of IL-26 overcame EGFR-TKI resistance in TNBC. Since the gene encoding IL-26 is absent in mice, we utilized human IL-26 transgenic (hIL-26Tg) mice as a tumor-bearing murine model to characterize the role of IL-26 in the differential effect of EGFR-TKI in human and mice and to confirm our in vitro findings. Our findings indicate that IL-26 activates the bypass pathway of EGFR-TKI, while blockade of IL-26 overcomes EGFR-TKI resistance in TNBC via enhancement of ER stress signaling. Our work provides novel insights into the mechanisms of EGFR-TKI resistance in TNBC via interaction of IL-26 with its newly identified receptor EphA3, while also suggesting IL-26 as a possible therapeutic target in TNBC.Subject terms: Stress signalling, Cell death and immune response, Breast cancer 相似文献
292.
A Tokoro K Suzuki T Matsumoto T Mikami S Suzuki M Suzuki 《Microbiology and immunology》1988,32(4):387-395
N-Acetyl chitohexaose (NACOS-6) was able to display chemotactic response of human neutrophils in vitro. In order to analyze the mechanism, a series of chemotaxis studies by means of neutrophils treated with inhibitors of phospholipase A2, cyclooxygenase, or lipoxygenase to NACOS-6 was conducted. The treatment of neutrophils with inhibitors of phospholipase A2 or cyclooxygenase resulted in decrease of number of migrated cells. However, the lipoxygenase inhibitors did not exhibit the same effect. On the other hand, the treatment of neutrophils with inhibitors of phospholipase A2 or lipoxygenase resulted in decrease of chemotactic response to Formyl-Met-Leu-Phe (FMLP), although the cyclooxygenase inhibitors did not inhibit chemotaxis of neutrophils. Neutrophils added to exogenous prostaglandin E2 (PGE2) caused an enhanced chemotactic response to NACOS-6. These results indicate that the mechanism of chemotactic response to NACOS-6 was different from that of FMLP, and that the response was enhanced by PGE2 released from the neutrophils with stimulation of NACOS-6. 相似文献
293.
G. S. Montes R. M. Krisztán K. M. Shigihara R. Tokoro P. A. S. Mourão L. C. U. Junqueira 《Histochemistry and cell biology》1980,65(2):131-141
Summary The results presented in this paper show that collagen fibers can be clearly distinguished from reticular fibers using the picrosirius-polarization method. A morphologic and morphometric study of these two types of fibers with electron microscopy shows that reticular fibers are characterized by the smaller diameter of their fibrillar components and the higher content of interfibrillar material, resulting in a loose arrangement of the fibrils. The evidences presented suggest that the amorphous matrix in which fibrils are embedded is responsible for the silver impregnation of reticular fibers. Our results show that the matrix of reticular fibers is characteristically rich in heparitin sulfate, and that the glycosaminoglycans present show a high interaction with the fibrillar component of these fibers. 相似文献