全文获取类型
收费全文 | 96篇 |
免费 | 8篇 |
出版年
2022年 | 2篇 |
2020年 | 1篇 |
2019年 | 1篇 |
2018年 | 1篇 |
2017年 | 1篇 |
2016年 | 3篇 |
2015年 | 2篇 |
2014年 | 8篇 |
2013年 | 6篇 |
2012年 | 9篇 |
2011年 | 9篇 |
2010年 | 7篇 |
2009年 | 6篇 |
2008年 | 5篇 |
2007年 | 4篇 |
2006年 | 10篇 |
2005年 | 4篇 |
2004年 | 3篇 |
2003年 | 4篇 |
2002年 | 4篇 |
1999年 | 1篇 |
1998年 | 1篇 |
1994年 | 1篇 |
1991年 | 3篇 |
1990年 | 2篇 |
1987年 | 1篇 |
1985年 | 1篇 |
1982年 | 1篇 |
1980年 | 1篇 |
1977年 | 1篇 |
1974年 | 1篇 |
排序方式: 共有104条查询结果,搜索用时 250 毫秒
11.
Ugurel S Schrama D Keller G Schadendorf D Bröcker EB Houben R Zapatka M Fink W Kaufman HL Becker JC 《Cancer immunology, immunotherapy : CII》2008,57(5):685-691
Purpose Chemokines influence both tumor progression and anti-tumor immune response. A 32-bp-deletion polymorphism in the chemokine
receptor 5 gene (CCR5Δ32) has been shown to result in a non-functional protein. This study was aimed at evaluating the potential
impact of this gene polymorphism on disease progression and treatment outcome in patients with melanoma.
Patients and methods CCR5 genotyping was performed by PCR on DNA extracted from serum samples of 782 cutaneous melanoma patients with known disease
history and long-term clinical follow-up. Genotypes were correlated with patient survival and types of treatment.
Results Of 782 melanoma patients, 90 (11.5%) were heterozygous and 12 (1.5%) were homozygous for CCR5Δ32. Analyzing the complete cohort,
the disease-specific survival from date of primary diagnosis was not influenced by CCR5 status. Similarly, no significant
impact could be detected on the treatment outcome of stage III patients. In 139 stage IV patients receiving immunotherapy,
CCR5Δ32 was associated with a decreased survival compared to patients not carrying the deletion (median 12.5 vs. 20.3 months,
P = 0.029). Multivariate analysis revealed the CCR5 genotype as an independent factor impacting disease-specific survival in
this patient population (P = 0.002), followed by gender (P = 0.019) and pathological classification of the primary (pT; P = 0.022).
Conclusion The presence of the CCR5Δ32 polymorphism in patients with stage IV melanoma results in a decreased survival following immunotherapy
and may help to select patients less likely to benefit from this type of treatment.
Selma Ugurel and David Schrama have contributed equally to this work. 相似文献
12.
13.
14.
Andersen K Mori H Fata J Bascom J Oyjord T Mælandsmo GM Bissell M 《Developmental biology》2011,352(2):581-190
High levels of the S100 calcium binding protein S100A4 also called fibroblast specific protein 1 (FSP1) have been established as an inducer of metastasis and indicator of poor prognosis in breast cancer. The mechanism by which S100A4 leads to increased cancer aggressiveness has yet to be established; moreover, the function of this protein in normal mammary gland biology has not been investigated. To address the role of S100A4 in normal mammary gland, its spatial and temporal expression patterns and possible function in branching morphogenesis were investigated. We show that the protein is expressed mainly in cells of the stromal compartment of adult humans, and during active ductal development, in pregnancy and in involution of mouse mammary gland. In 3D culture models, topical addition of S100A4 induced a significant increase in the TGFα mediated branching phenotype and a concomitant increase in expression of a previously identified branching morphogen, metalloproteinase-3 (MMP-3). These events were found to be dependent on MEK activation. Downregulation of S100A4 using shRNA significantly reduced TGFα induced branching and altered E-cadherin localization. These findings provide evidence that S100A4 is developmentally regulated and that it plays a functional role in mammary gland development, in concert with TGFα by activating MMP-3, and increasing invasion into the fat pad during branching. We suggest that S100A4-mediated effects during branching morphogenesis provide a plausible mechanism for how it may function in breast cancer progression. 相似文献
15.
16.
Mapatumumab and lexatumumab (targeting death receptor 4 (DR4) and 5 (DR5), respectively) are agonistic TRAIL receptor antibodies that induce apoptosis in a wide range of cancer cells. The potency of mapatumumab and lexatumumab was assessed in mono therapy protocols, and the ability to sensitize for dacarbazine (DTIC) treatment was explored in ten different melanoma cell lines. Our data indicated that melanoma cell lines tend to be resistant to mapatumumab, most likely due to low expression of DR4, while a dose dependent response to lexatumumab was observed. Combining DTIC and lexatumumab induced an additive or synergistic effect on cell death in the various melanoma cell lines. The synergistic effect observed in the FEMX-1 cell line was related to enhanced cleavage of Bid in parallel with elevated expression of the pro-apoptotic proteins Bim, Bax and Bak. Furthermore, the anti-apoptotic proteins Bcl-XL, cIAP-1, XIAP and livin were down regulated. Cleavage of Bid and down regulation of cIAP-2 and livin were observed in vivo. Altogether, these data suggest a change in the balance between pro- and anti-apoptotic proteins favoring induction of apoptosis. In the more therapy resistant cell line, HHMS, no changes in the pro- and anti-apoptotic proteins were observed. FEMX-1 xenografts treated with DTIC and lexatumumab showed reduced growth and increased level of apoptosis compared to the control groups, providing arguments for further evaluation of this combination in melanoma patients. 相似文献
17.
Marina Juraleviciute Joanna Pozniak Jrmie Nsengimana Mark Harland Juliette Randerson‐Moor Patrik Wernhoff Assia Bassarova Geir Frode
y Gunhild Tren Vivi Ann Flrenes David Timothy Bishop Meenhard Herlyn Julia Newton‐Bishop Ana Slipicevic 《Pigment cell & melanoma research》2020,33(3):446-457
MX2 protein is a dynamin‐like GTPase2 that has recently been identified as an interferon‐induced restriction factor of HIV‐1 and other primate lentiviruses. A single nucleotide polymorphism (SNP), rs45430, in an intron of the MX2 gene, was previously reported as a novel melanoma susceptibility locus in genome‐wide association studies. Functionally, however, it is still unclear whether and how MX2 contributes to melanoma susceptibility and tumorigenesis. Here, we show that MX2 is differentially expressed in melanoma tumors and cell lines, with most metastatic cell lines showing lower MX2 expression than primary melanoma cell lines and melanocytes. Furthermore, high expression of MX2 RNA in primary melanoma tumors is associated with better patient survival. Overexpression of MX2 reduces in vivo proliferation partially through inhibition of AKT activation, suggesting that it can act as a tumor suppressor in melanoma. However, we have also identified a subset of melanoma cell lines with high endogenous MX2 expression where downregulation of MX2 leads to reduced proliferation. In these cells, MX2 downregulation interfered with DNA replication and cell cycle processes. Collectively, our data for the first time show that MX2 is functionally involved in the regulation of melanoma proliferation but that its function is context‐dependent. 相似文献
18.
There is lack of studies investigating the association between bodyweight changes and health related quality of life (HRQL). The aim was to study the effect of relative changes in bodyweight over time on HRQL. In the Hordaland Health Study, 9276 men and 10433 women aged 40–47 years were included. Weight and height were measured and information on bodyweight changes during the last 5 years, physical activity and smoking was obtained from self–administered questionnaires including the Medical Outcomes Study MOS short form-12 including a Physical health Composite Score (PCS) and a Mental health Composite Score (MCS). Increasing bodyweight changes were associated with marked reduced scores in PCS and MCS also after adjustment for body mass index (BMI), physical activity and smoking. Men and women with a variation in weight with more than 15% during the last 5 years reported a mean score of MCS that was 0.48 standard deviation (SD) (3.9/8.1) and 0.35 SD (3.1/8.9) lower than those reporting a variation in weight less than 5%. No major differences were found between those who at date of examination were at the lower and higher end of the reported weight interval. There were no significant differences in the associations between men and women. Our findings confirm that increasing bodyweight changes are associated with reduced physical and mental health beyond what is related to BMI itself. 相似文献
19.
The hepatitis B virus PRE contains a splicing regulatory element 总被引:2,自引:0,他引:2
20.
Rosner K Röpke C Pless V Skovgaard GL 《Bioscience, biotechnology, and biochemistry》2006,70(9):2169-2177
No satisfactory treatment is currently available for metastatic malignant melanoma. Recently, the flavonoid quercetin was suggested as a potential treatment due to its anti-tumorogenic properties. Some of these properties appeared to correspond to those published for UVB irradiation. To determine quercetin's long-term effects, type of apoptosis, and shared properties with UVB, we exposed Mel-Juso, M14, and G361 human melanoma cell-lines to a large range of quercetin or UVB doses, 20-400 microm and 25-1000 mJ/cm2 respectively. Apoptosis was measured for 4 consecutive d by flow cytometry and cell viability was studied by colony-forming assay. Quercetin decreased cell viability level in a dose-dependent manner to almost zero at 100 microm. Up to this concentration, it did not induce significant apoptosis nor did it decrease the survival-fractions below 90% during a 4 d follow-up. The data suggest that Quercetin is lethal to melanoma cells at concentrations that do not activate apoptosis during the first 4 d post-exposure and that quercetin's effects extend beyond the period of direct contact. Both quercetin and UVB induced late-type apoptosis at the upper range of the tested doses, but they do not appear to share all the pathways that they activate. Finally, this paper provides novel data showing that quercetin causes two different lethal effects on human melanoma cells, suggesting the activation of at least two different dose-depended mechanisms. 相似文献