全文获取类型
收费全文 | 126篇 |
免费 | 23篇 |
出版年
2021年 | 1篇 |
2020年 | 1篇 |
2018年 | 2篇 |
2016年 | 1篇 |
2015年 | 3篇 |
2014年 | 2篇 |
2013年 | 9篇 |
2012年 | 10篇 |
2011年 | 6篇 |
2010年 | 7篇 |
2009年 | 8篇 |
2008年 | 5篇 |
2007年 | 1篇 |
2006年 | 10篇 |
2005年 | 5篇 |
2004年 | 4篇 |
2003年 | 6篇 |
2002年 | 1篇 |
2001年 | 3篇 |
2000年 | 2篇 |
1999年 | 3篇 |
1998年 | 4篇 |
1997年 | 2篇 |
1996年 | 4篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1993年 | 1篇 |
1992年 | 5篇 |
1991年 | 9篇 |
1990年 | 7篇 |
1989年 | 4篇 |
1988年 | 3篇 |
1987年 | 3篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1984年 | 1篇 |
1983年 | 3篇 |
1982年 | 1篇 |
1981年 | 1篇 |
1977年 | 2篇 |
1966年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有149条查询结果,搜索用时 15 毫秒
21.
Huang J Morehouse C Streicher K Higgs BW Gao J Czapiga M Boutrin A Zhu W Brohawn P Chang Y Viner J LaVallee T Richman L Jallal B Yao Y 《PloS one》2011,6(10):e26177
Purpose
Insulin-like growth factor (IGF) signaling through human insulin receptor isoform A (IR-A) contributes to tumorigenesis and intrinsic resistance to anti-IGF1R therapy. In the present study, we (a) developed quantitative TaqMan real time-PCR-based assays (qRT-PCR) to measure human insulin receptor isoforms with high specificity, (b) evaluated isoform expression levels in molecularly-defined breast cancer subtypes, and (c) identified the IR-A:IR-B mRNA ratio as a potential biomarker guiding patient stratification for anti-IGF therapies.Experimental Design
mRNA expression levels of IR-A and IR-B were measured in 42 primary breast cancers and 19 matched adjacent normal tissues with TaqMan qRT-PCR assays. The results were further confirmed in 165 breast cancers. The tumor samples were profiled using whole genome microarrays and subsequently subtyped using the PAM50 breast cancer gene signature. The relationship between the IR-A:IR-B ratio and cancer subtype, as well as markers of proliferation were characterized.Results
The mRNA expression levels of IR-A in the breast tumors were similar to those observed in the adjacent normal tissues, while the mRNA levels of IR-B were significantly decreased in tumors. The IR-A:IR-B ratio was significantly higher in luminal B breast cancer than in luminal A. Strong concordance between the IR-A:IR-B ratio and the composite Oncotype DX proliferation score was observed for stratifying the latter two breast cancer subtypes.Conclusions
The reduction in IR-B expression is the key to the altered IR-A:IR-B ratio observed in breast cancer. The IR-A:IR-B ratio may have biomarker utility in guiding a patient stratification strategy for an anti-IGF therapeutic. 相似文献22.
J B Takahashi M Hoshimaru M Jaye H Kikuchi M Hatanaka 《Biochemical and biophysical research communications》1992,189(1):398-405
Acidic and basic fibroblast growth factors (aFGF and bFGF) are mitogens for mesoderm- and neuroectoderm-derived cells. The facts that FGF-related proteins are oncogenic and that FGFs are expressed in a variety of tumor cell lines or tumor tissues suggest the transforming activities of FGFs. To examine such an activity of aFGF, we introduced a human aFGF expression vector into two populations of Rat-1 cells; one was non-transformed (nRat-1), the other was partially-transformed (tRat-1). tRat-1 cells transfected with aFGF cDNA formed larger colonies in soft agar and produced larger and more malignant tumors in nude mice than those of parental cells. In contrast, nRat-1 cells transfected with aFGF cDNA neither formed colonies in soft agar nor produced tumors in nude mice. Our results suggest that high expression of aFGF may enhance a tumorigenic potential of Rat-1 cells rather than confer such a potential de novo. 相似文献
23.
24.
25.
Antigen-Specific Expansion of Cytotoxic T Lymphocytes in Acute Measles Virus Infection 总被引:6,自引:3,他引:3 下载免费PDF全文
Juthathip Mongkolsapaya Assan Jaye Margaret F. C. Callan Albert F. Magnusen Andrew J. McMichael Hilton C. Whittle 《Journal of virology》1999,73(1):67-71
Skewing of the T-cell receptor repertoire of CD8+ T cells has been shown in some persistent infections with viruses, such as human immunodeficiency virus, simian immunodeficiency virus, and Epstein-Barr virus. We have demonstrated that similar distortions also occur in nonpersistent measles virus infection. In addition, two of four children immunized with live, attenuated measles virus showed larger and more persistent CD8+ T-cell expansions than their naturally infected counterparts. The expanded lymphocyte populations were monoclonal or oligoclonal and lysed target cells infected with recombinant vaccinia virus expressing measles virus protein. These results demonstrate that the expansions of CD8+ T lymphocytes are antigen driven. 相似文献
26.
27.
Joseph P. Marino Lara S. Kallander Chun Ma Hye-Ja Oh Dennis Lee Dimitri E. Gaitanopoulos John A. Krawiec Derek J. Parks Christine L. Webb Kelly Ziegler Michael Jaye Scott K. Thompson 《Bioorganic & medicinal chemistry letters》2009,19(19):5617-5621
The liver X receptors (LXR) play a key role in cholesterol homeostasis and lipid metabolism. SAR studies around tertiary-amine lead molecule 2, an LXR full agonist, revealed that steric and conformational changes to the acetic acid and propanolamine groups produce dramatic effects on agonist efficacy and potency. The new analogs possess good functional activity, demonstrating the ability to upregulate LXR target genes, as well as promote cholesterol efflux in macrophages. 相似文献
28.
In the United States, disease screening is offered to the public as a consumer service. It has been proposed that the act
of “consumption” is a manifestation of agency and that the decision to consume is an exercise of autonomy. The enthusiasm
of the American public for disease screening and the expansion in the demand for all sorts of disease screening in recent
years can be viewed as an expression of such autonomy. Here, we argue that the enthusiasm for disease screening witnessed
in the American public today may be more a reflection of the constraint on autonomy than its facilitation. It is our opinion
that the articulation of socio-historical processes has contributed to a moral imperative which is reflected in the decision
making of individuals around disease screening. We suggest medical and health professionals have a responsibility to facilitate
the exercise of individual autonomy in health care decision making as an integral component of professional obligation. These
professionals need to problematise healthcare activities that constrain individual autonomy. 相似文献
29.
30.
Kevin J. Woollard Natalie G. Lumsden Karen L. Andrews Andrea Aprico Emma Harris Jennifer C. Irvine Ann-maree Jefferis Lu Fang Peter Kanellakis Alex Bobik Jaye P. F. Chin-Dusting 《PloS one》2014,9(5)
Soluble P-selectin (sP-selectin), a biomarker of inflammatory related pathologies including cardiovascular and peripheral vascular diseases, also has pro-atherosclerotic effects including the ability to increase leukocyte recruitment and modulate thrombotic responses in vivo. The current study explores its role in progressing atherosclerotic plaque disease. Apoe
−/− mice placed on a high fat diet (HFD) were given daily injections of recombinant dimeric murine P-selectin (22.5 µg/kg/day) for 8 or 16 weeks. Saline or sE-selectin injections were used as negative controls. In order to assess the role of sP-selectin on atherothrombosis an experimental plaque remodelling murine model, with sm22α-hDTR Apoe−/− mice on a HFD in conjunction with delivery of diphtheria toxin to induce targeted vascular smooth muscle apoptosis, was used. These mice were similarly given daily injections of sP-selectin for 8 or 16 weeks. While plaque mass and aortic lipid content did not change with sP-selectin treatment in Apoe−/− or SM22α-hDTR Apoe−/− mice on HFD, increased plasma MCP-1 and a higher plaque CD45 content in Apoe
−/− HFD mice was observed. As well, a significant shift towards a more unstable plaque phenotype in the SM22α-hDTR Apoe−/− HFD mice, with increased macrophage accumulation and lower collagen content, leading to a lower plaque stability index, was observed. These results demonstrate that chronically raised sP-selectin favours progression of an unstable atherosclerotic plaque phenotype. 相似文献