全文获取类型
收费全文 | 412篇 |
免费 | 21篇 |
国内免费 | 5篇 |
专业分类
儿科学 | 16篇 |
妇产科学 | 4篇 |
基础医学 | 52篇 |
口腔科学 | 11篇 |
临床医学 | 26篇 |
内科学 | 49篇 |
皮肤病学 | 2篇 |
神经病学 | 26篇 |
特种医学 | 51篇 |
外科学 | 14篇 |
综合类 | 7篇 |
预防医学 | 10篇 |
眼科学 | 3篇 |
药学 | 21篇 |
肿瘤学 | 146篇 |
出版年
2023年 | 2篇 |
2022年 | 2篇 |
2021年 | 11篇 |
2020年 | 4篇 |
2019年 | 7篇 |
2018年 | 2篇 |
2017年 | 4篇 |
2016年 | 5篇 |
2015年 | 15篇 |
2014年 | 35篇 |
2013年 | 16篇 |
2012年 | 18篇 |
2011年 | 18篇 |
2010年 | 17篇 |
2009年 | 7篇 |
2008年 | 16篇 |
2007年 | 18篇 |
2006年 | 21篇 |
2005年 | 25篇 |
2004年 | 17篇 |
2003年 | 13篇 |
2002年 | 10篇 |
2001年 | 11篇 |
2000年 | 4篇 |
1999年 | 4篇 |
1998年 | 20篇 |
1997年 | 17篇 |
1996年 | 16篇 |
1995年 | 8篇 |
1994年 | 9篇 |
1993年 | 16篇 |
1992年 | 4篇 |
1991年 | 5篇 |
1990年 | 3篇 |
1989年 | 9篇 |
1988年 | 6篇 |
1987年 | 4篇 |
1986年 | 3篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1983年 | 3篇 |
1981年 | 1篇 |
1980年 | 2篇 |
1979年 | 1篇 |
1977年 | 2篇 |
1976年 | 2篇 |
排序方式: 共有438条查询结果,搜索用时 15 毫秒
31.
Background
We previously identified brain type fatty acid-binding protein (FABP7) as a prognostic marker for patients with glioblastoma (GBM). Increased expression of FABP7 is associated with reduced survival. To investigate possible molecular mechanisms underlying this association, we compared the expression and subcellular localization of FABP7 in non-tumor brain tissues with different types of glioma, and examined the expression of FABP7 and epidermal growth factor receptor (EGFR) in GBM tumors. 相似文献32.
33.
34.
McDonald JM See SJ Tremont IW Colman H Gilbert MR Groves M Burger PC Louis DN Giannini C Fuller G Passe S Blair H Jenkins RB Yang H Ledoux A Aaron J Tipnis U Zhang W Hess K Aldape K 《Cancer》2005,104(7):1468-1477
BACKGROUND: It has been reported previously that the combined loss of chromosomal arms 1p and 19q is a significant predictor of outcome for patients with anaplastic oligodendroglial (AO) tumors and that such chromosomal loss correlates with classic histology in AO. The authors sought to determine whether histology was an equivalent or superior predictor of outcome compared with 1p/19q status in 131 patients with AO tumors. METHODS: The status of 1p and 19q was determined using real-time, quantitative polymerase chain reaction analysis and/or fluorescence in situ hybridization. Clinical features (response to adjuvant therapy and tumor location) and molecular genetic abnormalities (9p and 10q deletions, overexpression of p53 and epidermal growth factor receptor) were determined on available specimens. Histologic assessments for classic oligodendroglial features were performed by five neuropathologists. RESULTS: Classic histology was associated closely with 1p/19q loss, as reported previously. Patients who had tumors that were considered classic by at least four of the five neuropathologists showed significantly increased progression-free and overall survival compared with the patients who had less classic tumors. The authors also tested the correlation between 1p/19q status and outcome in subsets of patients stratified according to classic tumor features. The association of 1p/19q status with survival was related closely to the presence of classic histology. Loss of 1p/19q was predictive of improved outcome only among patients who had tumors with classic histologic features. CONCLUSIONS: The current results suggested that, in addition to 1p/19q status, histologic features contribute information to the prediction of outcome in patients with AO. Loss of 1p and 19q appeared to be a prognostic marker only in the subset of patients who had AO tumors with classic histologic features. 相似文献
35.
Ribalta T McCutcheon IE Aldape KD Bruner JM Fuller GN 《The American journal of surgical pathology》2004,28(11):1532-1536
Mitotic figure (MF) counting is the most objective criterion for grading of meningiomas according to the 2000 World Health Organization (WHO) classification. However, the search for the area(s) of highest mitotic activity is tedious, and there is high interobserver variability in differentiating MF from apoptotic cells. We tested the utility of the mitosis-specific marker phosphohistone-H3 (PHH3) to enhance rapid recognition of MFs and quick reliable grading of meningioma. Fifty-four archival meningiomas (26 benign, 20 atypical, 8 anaplastic) were reclassified according to current WHO criteria. PHH3-immunostained MFs were counted the same way as in hematoxylin and eosin-stained sections. Anti-PHH3-labeled MFs were easily seen and permitted quick identification of the area(s) of highest mitotic activity. Count results (mean) show a strong correlation between both methods: benign, hematoxylin and eosin 1.4, PHH3 2.2; atypical, hematoxylin and eosin 9.0, PHH3 15.9; anaplastic, hematoxylin and eosin 22.4, PHH3 34.1. PHH3 counting yielded greater sensitivity and in 12 cases (22.2%) suggested a change in grade (increased 9; lowered 3). All cases in which PHH3 lowered the grade were from older blocks, suggesting a loss of antigen preservation. PHH3 immunostaining facilitates the rapid reliable grading of meningiomas by focusing attention on the most mitotically active areas and by allowing easy and objective differentiation of MFs from apoptotic nuclei. 相似文献
36.
Loss of heterozygosity of chromosome 3p21 is associated with mutant TP53 and better patient survival in non-small-cell lung cancer 总被引:2,自引:0,他引:2
Marsit CJ Hasegawa M Hirao T Kim DH Aldape K Hinds PW Wiencke JK Nelson HH Kelsey KT 《Cancer research》2004,64(23):8702-8707
Allelic loss of chromosome region 3p21.3 occurs early and frequently in non-small-cell lung cancer, and numerous tumor suppressor genes at this locus may be targets of inactivation. Using an incident case series study of non-small-cell lung cancer, we sought to determine the prevalence of loss of heterozygosity (LOH) in the 3p21.3 region and to examine the associations between this alteration and patient outcome, exposure to tobacco smoke, occupational asbestos exposure, and additional molecular alterations in these tumors. We examined LOH at 7 microsatellite markers in the chromosome 3p21.3 region, and LOH was present in at least one of the loci examined in 60% (156 of 258) of the tumors, with the prevalence of LOH at individual loci ranging from 15 to 56%. Occupational asbestos exposure and TP53 mutation were significantly associated with more extensive 3p21 LOH. In squamous cell carcinomas, measures of cumulative smoking dose were significantly lower in patients with LOH at 3p21, particularly in TP53 mutant tumors. Examining patient outcome, we found that in squamous cell carcinomas, having any LOH in this region was associated with a better overall survival (log-rank test, P < 0.04). Together, these results indicate that allelic loss at 3p21 can affect patient outcome, and that this loss may initially be related to carcinogen exposure, but that extension of this loss is related to TP53 mutation status and occupational asbestos exposure. 相似文献
37.
38.
Soroceanu L Kharbanda S Chen R Soriano RH Aldape K Misra A Zha J Forrest WF Nigro JM Modrusan Z Feuerstein BG Phillips HS 《Proceedings of the National Academy of Sciences of the United States of America》2007,104(9):3466-3471
Amplification or overexpression of growth factor receptors is a frequent occurrence in malignant gliomas. Using both expression profiling and in situ hybridization, we identified insulin-like growth factor 2 (IGF2) as a marker for a subset of glioblastomas (GBMs) that lack amplification or overexpression of EGF receptor. Among 165 primary high-grade astrocytomas, 13% of grade IV tumors and 2% of grade III tumors expressed IGF2 mRNA levels >50-fold the sample population median. IGF2-overexpressing tumors frequently displayed PTEN loss, were highly proliferative, exhibited strong staining for phospho-Akt, and belonged to a subclass of GBMs characterized by poor survival. Using a serum-free culture system, we discovered that IGF2 can substitute for EGF to support the growth of GBM-derived neurospheres. The growth-promoting effects of IGF2 were mediated by the insulin-like growth factor receptor 1 and phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3), a regulatory subunit of phosphoinositide 3-kinase that shows genomic gains in some highly proliferative GBM cases. PIK3R3 knockdown inhibited IGF2-induced growth of GBM-derived neurospheres. The current results provide evidence that the IGF2-PIK3R3 signaling axis is involved in promoting the growth of a subclass of highly aggressive human GBMs that lack EGF receptor amplification. Our data underscore the importance of the phosphoinositide 3-kinase/Akt pathway for growth of high-grade gliomas and suggest that multiple molecular alterations that activate this signaling cascade may promote tumorigenesis. Further, these findings highlight the parallels between growth factors or receptors that are overexpressed in GBMs and those that support in vitro growth of tumor-derived stem-like cells. 相似文献
39.
Life-threatening Clostridium sordellii infections have recently been reported in women undergoing therapeutic abortion, during natural childbirth, and in injection drug users. Shock, diffuse capillary leak, and a leukemoid reaction (LR) are cardinal features of these infections. The magnitude of the LR is highly correlated with mortality. We have isolated a 42-kDa extractable protein from C. sordellii culture supernatant that stimulates proliferation of promyelocytic HL-60 cells in vitro. Using mass spectrometry, we have identified this protein as the C. sordellii neuraminidase, NanS. Recombinant NanS (rNanS) dose dependently stimulated HL-60 cell proliferation. Increased proliferation was observed when HL-60 cells were cocultured with both rNanS and granulocyte-macrophage colony stimulating factor. In addition, NanS also modified vascular cell adhesion molecule 1, which orchestrates the release of mature and immature granulocytes from bone marrow stromal cells. Thus, neuraminidase likely plays an important role in the characteristic LR in C. sordellii infection. 相似文献
40.
KD McCloskey UA Anderson RA Davidson YR Bayguinov KM Sanders SM Ward 《British journal of pharmacology》2009,156(2):273-283