全文获取类型
收费全文 | 188篇 |
免费 | 21篇 |
出版年
2018年 | 2篇 |
2017年 | 1篇 |
2016年 | 1篇 |
2015年 | 13篇 |
2014年 | 11篇 |
2013年 | 13篇 |
2012年 | 7篇 |
2011年 | 9篇 |
2010年 | 12篇 |
2009年 | 8篇 |
2008年 | 15篇 |
2007年 | 10篇 |
2006年 | 8篇 |
2005年 | 9篇 |
2004年 | 9篇 |
2003年 | 3篇 |
2002年 | 5篇 |
2001年 | 4篇 |
2000年 | 6篇 |
1999年 | 5篇 |
1998年 | 7篇 |
1997年 | 3篇 |
1996年 | 4篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1992年 | 1篇 |
1991年 | 3篇 |
1990年 | 6篇 |
1989年 | 3篇 |
1988年 | 4篇 |
1987年 | 2篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1983年 | 3篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1977年 | 2篇 |
1976年 | 1篇 |
1970年 | 1篇 |
排序方式: 共有209条查询结果,搜索用时 15 毫秒
21.
Background
A recent epidemiological study demonstrated a reduced risk of lung cancer mortality in breast cancer patients using antiestrogens. These and other data implicate a role for estrogens in lung cancer, particularly nonsmall cell lung cancer (NSCLC). Approximately 61% of human NSCLC tumors express nuclear estrogen receptor β (ERβ); however, the role of ERβ and estrogens in NSCLC is likely to be multifactorial. Here we tested the hypothesis that proteins interacting with ERβ in human lung adenocarcinoma cells that respond proliferatively to estradiol (E2) are distinct from those in non-E2-responsive cells.Methods
FLAG affinity purification of FLAG-ERβ-interacting proteins was used to isolate ERβ-interacting proteins in whole cell extracts from E2 proliferative H1793 and non-E2-proliferative A549 lung adenocarcinoma cell lines. Following trypsin digestion, proteins were identified using liquid chromatography electrospray ionization tandem mass spectrometry (LC-MS/MS). Proteomic data were analyzed using Ingenuity Pathway Analysis. Select results were confirmed by coimmunoprecipitation.Results
LC-MS/MS identified 27 non-redundant ERβ-interacting proteins. ERβ-interacting proteins included hsp70, hsp60, vimentin, histones and calmodulin. Ingenuity Pathway Analysis of the ERβ-interacting proteins revealed differences in molecular and functional networks between H1793 and A549 lung adenocarcinoma cells. Coimmunoprecipitation experiments in these and other lung adenocarcinoma cells confirmed that ERβ and EGFR interact in a gender-dependent manner and in response to E2 or EGF. BRCA1 interacted with ERβ in A549 cell lines and in human lung adenocarcinoma tumors, but not normal lung tissue.Conclusion
Our results identify specific differences in ERβ-interacting proteins in lung adenocarcinoma cells corresponding to ligand-dependent differences in estrogenic responses.22.
Background
Designing maximally selective ligands that act on individual targets is the dominant paradigm in drug discovery. Poor selectivity can underlie toxicity and side effects in the clinic, and for this reason compound selectivity is increasingly monitored from very early on in the drug discovery process. To make sense of large amounts of profiling data, and to determine when a compound is sufficiently selective, there is a need for a proper quantitative measure of selectivity. 相似文献23.
Létuvé S Kozhich A Arouche N Grandsaigne M Reed J Dombret MC Kiener PA Aubier M Coyle AJ Pretolani M 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(7):5167-5173
YKL-40 is a chitin-binding protein that is elevated in patients with various inflammatory conditions associated with ongoing remodeling. We investigated whether the levels of YKL-40 were up-regulated in the circulation and the airways of patients with chronic obstructive pulmonary disease (COPD), and whether it promoted the production of inflammatory mediators from macrophages. Serum, bronchoalveolar lavage (BAL), bronchial biopsies, lung tissue specimens, and alveolar macrophages from never-smokers (n = 15), smokers without COPD (n = 20), and smokers with COPD (n = 30) were assessed for YKL-40 levels and immunolocalization. In addition, YKL-40-induced mediator release from alveolar macrophages was examined. We found that smokers with COPD had elevated levels of YKL-40 in serum (p = 0.027) and BAL (p = 0.007), more YKL-40-positive cells in bronchial biopsies (p = 0.03), and a greater proportion of alveolar macrophages expressing YKL-40 than smokers without COPD or never-smokers. YKL-40 levels in serum and BAL were associated with airflow obstruction (pre-beta(2) agonist forced expiratory volume in 1 s, r(s) = -0.3892, p = 0.0072 and r(s) = -0.5491, p < 0.0001, respectively) and impaired diffusion lung capacity (transfer factor of the lung for carbon monoxide, r(s) = -0.4667, p = 0.002 and r(s) = -0.3854, p = 0.0045, respectively). TNF-alpha stimulated YKL-40 synthesis in alveolar macrophages from smokers with COPD, and exposure of these cells to YKL-40 promoted the release of IL-8, MCP-1, MIP-1alpha, and metalloproteinase-9. We conclude that YKL-40 is up-regulated in COPD, in which it may contribute to tissue inflammation and remodeling by sustaining the synthesis of proinflammatory and fibrogenic chemokines and of metalloproteinases by alveolar macrophages. 相似文献
24.
Background
Immune response pathways have been relatively well-conserved across animal species, with similar systems in both mammals and invertebrates. Interestingly, honey bees have substantially reduced numbers of genes associated with immune function compared with solitary insect species. However, social species such as honey bees provide an excellent environment for pathogen or parasite transmission with controlled environmental conditions in the hive, high population densities, and frequent interactions. This suggests that honey bees may have developed complementary mechanisms, such as behavioral modifications, to deal with disease. 相似文献25.
Wenhui Nie Beiyuan Fu Patricia CM O'Brien Jinhuan Wang Weiting Su Alongkoad Tanomtong Vitaly Volobouev Malcolm A Ferguson-Smith Fengtang Yang 《BMC biology》2008,6(1):18
Background
Flying lemurs or Colugos (order Dermoptera) represent an ancient mammalian lineage that contains only two extant species. Although molecular evidence strongly supports that the orders Dermoptera, Scandentia, Lagomorpha, Rodentia and Primates form a superordinal clade called Supraprimates (or Euarchontoglires), the phylogenetic placement of Dermoptera within Supraprimates remains ambiguous. 相似文献26.
TJP3/ZO-3 is a scaffolding protein that tethers tight junction integral membrane proteins to the actin cytoskeleton and links the conserved Crumbs polarity complex to tight junctions. The physiological function of TJP3/ZO-3 is not known and mice lacking TJP3/ZO-3 show no apparent phenotype. Here we show that Tjp3/Zo-3 is a component of tight junctions present in the enveloping cell layer of zebrafish embryos. Silencing tjp3/zo-3 using morpholinos leads to edema, loss of blood circulation and tail fin malformations in the embryos. The ultrastructure of tight junctions of the enveloping cell layer is disrupted, without affecting the asymmetric distribution of plasma membrane proteins. Morphants show a loss of the epidermal barrier, as assessed by an increased permeability of the enveloping cell layer to low molecular weight tracers and a higher sensitivity of the embryos to osmotic stress. Subjecting wild-type embryos to osmotic stress mimicks the morphant phenotype, consistent with the phenotype being a direct consequence of failed osmoregulation. Thus, Tjp3/Zo-3 is critical for barrier function of the enveloping cell layer and osmoregulation in early stages of zebrafish development. 相似文献
27.
28.
Helmut R. Salih Gary C. Starling Markus Knauff Maj-Britt Llewellyn Patricia M. Davis William J. Pitts Alejandro Aruffo Peter A. Kiener 《Experimental cell research》2001,270(2):248-258
CD178 (CD95-ligand) is expressed on several tumor cells and likely influences the interaction of the tumor with the host immune system. However, little is known about the mechanisms that regulate its expression on the cell surface. We have evaluated the ability of various compounds and cytokines to regulate cell surface expression and release of soluble CD178 in various carcinoma cell lines. Vitamin E succinate (VES) and retinoic acid (RA) were found to reduce CD178 surface expression, whereas interferon-gamma stimulated a slight upregulation. At 48 h, the regulation of surface CD178 by VES and RA arose from a small decrease in CD178 mRNA and to a greater extent due to an increase in the release of soluble CD178; the latter was blocked by addition of a metalloproteinase inhibitor. Accordingly, VES and RA treatment diminished the ability of tumor cells to kill CD95-sensitive cells and this effect was markedly reduced by the presence of a metalloproteinase inhibitor. Our results indicate that, in vitro, CD178 expression on the cell surface of tumor cells can be regulated by agents that alter both expression and release of the ligand. In vivo, such treatments may play an important role in the outcome of tumor sensitivity or resistance to host immune mechanisms. 相似文献
29.
R S Mittler C A Fifer P Burbach K Edinger P A Kiener 《Journal of immunology (Baltimore, Md. : 1950)》1990,145(3):794-803
We describe the requirements for T cell activation by a mAb termed 4-10 that recognizes a novel determinant on MHC class I molecules. The determinant recognized by mAb 4-10 appears on resting T cells of all individuals tested (n greater than 30). Unlike previously described anti-class I mAb, 4-10 was shown to be directly mitogenic for T cells obtained from more than 20 normal donors. In order for 4-10 to exert its mitogenic effect on purified T cell populations it must be immobilized on a solid support. Immobilization of 4-10 can be circumvented if low numbers of adherent cells are added to the T cell cultures. mAb 4-10 preferentially activates the CD8+ T cell subset as judged by the fact that CD8+ T cells preferentially down-regulated their TCR after 4-10 activation and because CD4+ T cell activation with 4-10 requires approximately five times the concentration of mAb needed to reach comparable levels of activation observed with CD8+ T cells. We further observed that simultaneous cross-linking of class I and CD8 Ag by using 4-10 and anti-CD8 mAb almost completely abrogated the proliferative response of T cells when anti-CD8 was presented in immobilized form. In contrast, similar cross-linking with 4-10 and anti-CD4 diminished the response by about 20%. We also found that other anti-class I mAb were able to synergize in the activation of T cells with mAb 4-10 in a dose-dependent manner. 相似文献
30.
Retrotransposon BARE-1 and Its Role in Genome Evolution in the Genus Hordeum. 总被引:11,自引:0,他引:11
下载免费PDF全文
![点击此处可从《The Plant cell》网站下载免费的PDF全文](/ch/ext_images/free.gif)
CM Vicient A Suoniemi K Anamthawat-Jnsson J Tanskanen A Beharav E Nevo AH Schulman 《The Plant cell》1999,11(9):1769-1784