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21.
Background Seprase plays an important role in malignant cell invasion and metastasis by degrading the extracellular matrix. However, its clinical significance remains largely unknown. The objective of the current study was to evaluate the expression of seprase in effusions from patients with epithelial ovarian carcinoma and its clinical values. Methods Immunohistochemistry was used to examine the expression of seprase protein in a series of 74 malignant peritoneal (n=64) and pleural (n=10) effusions from Norwegian patients with epithelial ovarian carcinoma. Additionally, 34 effusions were evaluated using the Western blotting. Nine reactive effusions, obtained from patients with benign lesions, served as a control group. Statistical analyses were carried out by Chi-square test and Kaplan-Meier method. Results In the 74 malignant effusion specimens, 57 (77.02%) were positive for seprase, while only 2 (22.22%) of the control group were positively stained (P=-0.001). In the malignant effusions, 17 (22.97%), 22 (29.73%), 22 (29.73%), 13 (17.57%) had negative, weak, moderate and strong seprase protein expression, respectively. The expression of seprase protein was predominant in cytoplasm of carcinoma cells. Increased seprase protein was negatively associated with the overall survival rate of the patients (P=0.03). However, there was no significant correlation between protein expression and FIGO stage, age, histology, and histological grade. By Western blotting, 27 of the 34 effusions showed the presence of both 170-kD dimeric form and 97-KD monomeric form of seprase while only 1 of the 34 had 170-KD dimeric form, which was consistent with the results of immunohistochemistry (P=0.05). Conclusions Seprase may be involved in the development of ovarian cancer, and is a potential predictive marker for the disease.  相似文献   
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Non-membranous beta-catenin and gamma-catenin, c-Myc and cyclin D1 are key participants in the Wnt cell signalling pathway, in which aberrancies have been associated with malignant cell transformation. We assessed the independent prognostic value of these proteins in a clinical material. Tumours from a series of 162 patients operated on for Dukes' stage A, B and C colonic adenocarcinomas were analysed using semiquantitative immunohistochemistry and the results were related to patient outcome. Patients expressing nuclear beta-catenin in the primary tumour showed reduced survival compared to other patients (log rank p=0.028) and there was also an association with development of metastases follow-up (logistic regression p=0.024). Using multivariate analysis (Cox regression) co-expression of nuclear beta-catenin and c-Myc turned out to be the strongest marker of impaired prognosis (p=0.001, HR 5.26, 95% CI 1.93-14.36). Expression of non-membranous gamma-catenin, cyclin D1 and c-Myc alone failed to have independent prognostic significance in our study.  相似文献   
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A number of studies have emphasized the role of PAI-1 as an important regulator of tumor cell invasion and metastasis. The hallmark of primary tumors of the central nervous system and glioblastomas in particular is the diffuse invasion into the normal brain tissue. Since PAI-1 is expressed in such tumors, we studied the effect of adenoviral-mediated transfer of the PAI-1 gene in regulating the in vitro invasiveness of D54Mg glioma cells into Matrigel, and into fetal rat brain aggregates. Treatment of D54Mg cells with 50 MOI (multiplicity of infection) of the replication defective vector AdCMVPAI-1 increased PAI-1 expression 23-fold compared to control vectors, and the invasion through Matrigel was reduced by 67%. The motility of the cells was reduced by 58% compared to controls (indicating that inhibition of motility was the principal effect of PAI-1 in these cells). The ability of D54Mg tumor spheroids to invade fetal rat brain aggregates was not reduced by the PAI-1 gene transfer. The results show that overexpression of PAI-1 can inhibit glioma cell motility and invasion through extracellular matrix (ECM) components, like laminin and collagen, but does not inhibit tumor cell invasion in a three-dimensional invasion assay, simulating normal brain tissue having a different ECM and interstitial composition. The different results obtained in the two invasion assays reflect the complex biological effects of the uPA/PAI-1 system, and questions a simplistic view of PAI-1 as an inhibitor of brain tumor invasion. This revised version was published online in July 2006 with corrections to the Cover Date.  相似文献   
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OBJECTIVE: The objective was to investigate the expression (level) and phosphorylation status (activity) of the extracellular-regulated kinase (ERK), c-Jun amino-terminal kinase (JNK), and high-osmolarity glycerol response kinase (p38), their role in the biology of ovarian carcinoma, and their correlation with chemotherapy response. METHODS: Sixty-four fresh-frozen effusions from patients diagnosed with serous ovarian carcinoma were studied using immunoblotting. Results were analyzed for possible association with expression of proliferation and apoptosis markers, patient age, disease stage, tumor grade, histological grade, chemotherapy status, and survival. RESULTS: p38 level correlated with younger age (P = 0.004), while that of JNK correlated with better tumor differentiation (P = 0.009). Higher expression of Pan-JNK (P = 0.018) and higher p-ERK activity (P = 0.014) were seen in postchemotherapy specimens, specifically related to treatment by platinum agents. pan-JNK expression was higher in specimens treated with both platinum agents (P = 0.038) and paclitaxel (P = 0.033). In univariate survival analysis, the level of pan-ERK (P = 0.002), pan-JNK (P = 0.045), and pan-p38 (P = 0.016), as well as p-ERK activity (P = 0.014) correlated with better overall survival. In Cox multivariate survival analysis, pan-ERK (P = 0.001), pan-p38 (P = 0.017), and p-ERK (P = 0.041) retained their predictive value. CONCLUSIONS: Our results present the first evidence of in vivo involvement of MAPKs in the clinical course of ovarian cancer and the possible effect of chemotherapy on intracellular signaling in this disease. The improved prognosis associated with expression and phosphorylation of all three mitogen-activated protein kinase families highlights the unique properties of cancer cells in effusions and may expand our understanding of the biology of ovarian carcinoma at this site, possibly affecting treatment strategies for this malignancy.  相似文献   
27.
Expression of EGF, HB-EGF, TGF-alpha, HRG-alpha, HRG-beta1, and HRG-beta3 in 100 frozen breast carcinoma materials was immunohistochemically studied. Among these tumors, 67% were positive for EGF, 53% for HB-EGF, 57% for TGF-alpha, 60% for HRG-alpha, 53% for HRG-beta1, and 63% for HRG-beta3 in the neoplastic epithelial cells. No significant associations between expression of the growth factors and clinicopathological features like tumor size, histologic grade, node status, ploidy, ER status, and c-erbB-4 expression were observed, with the exceptions that significant relations were present between EGF expression and tumor size (p = 0.01) and between HRG-beta3 expression and node status (p = 0.02). The expressions of these growth factors showed no association with cancer-specific survival by the Kaplan Meier analysis.  相似文献   
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Breast hypoplasia is encountered as part of genetic syndromes or as a result of iatrogenic factors. The incidence of this malformation and the occurrence of breast carcinoma in such cases are unknown. The authors present a 66-year-old patient with a severe breast hypoplasia and invasive lobular carcinoma. The advanced clinical stage required neoadjuvant chemotherapy. After 5 CMF cycles with no significant effect, a modified radical mastectomy with axillary lymph node dissection was performed. The pathological report revealed an infiltrating lobular carcinoma with combined classical and alveolar growth and with minor morphological changes after the chemotherapy. Immunostaining for cell proliferation markers, apoptotic regulators, and cell adhesion molecules, such as the CD44 family and members of the cadherin-catenin group, was performed. The tumor expressed a high bcl-2/low bax ratio and lacked p53 immunoreactivity, which could explain the resistance to neoajuvant therapy. The lack of adhesion molecules, except for strong E-cadherin and β-catenin reactivity, and weak CD44v6 expression were demonstrated. To the authors' knowledge this is the first case of an invasive lobular carcinoma in a hypoplastic breast reported in the English literature.  相似文献   
29.
One of the most studied onco-gene families in breast tumors is the type 1 protein tyrosine kinase family, which consists of EGFR, c-erbB-2, c-erbB-3, and c-erbB-4. Overexpression of c-erbB-2 protein/mRNA in breast carcinomas is consistently associated with poor prognosis, while EGFR overexpression has been confirmed to have a synergistic clinical effect on the c-erbB-2 influence. The expression pattern of c-erbB-4 in breast carcinomas is special. Unlike other type 1 protein tyrosine kinases, expression of c-erbB-4 protein/mRNA is reduced in carcinomas compared with that in normal breast epithelia, and its expression has also been associated with a better clinical outcome, indicating the need for c-erbB-4 analysis when clinical therapeutic application of EGFR and c-erbB-2 anitbodies is considered. In addition, studies of the adaptor proteins in breast carcinomas are highly indicated in order to clarify the mechanisms behind the dysregulated expression of such receptors in breast carcinomas.  相似文献   
30.
Imbalance between pro-apoptotic and anti-apoptotic proteins, causing altered apoptosis, may lead to tumour development and tumour progression, and reduced response to adjuvant therapy. In this study, we evaluated the expression patterns of Bcl-2, Bcl-xL, and Bax protein in 126 primary invasive breast carcinomas, and the association with other clinicopathological parameters. We used immunohistochemical methods to evaluate protein expression. Reduced expression of both Bax and Bcl-2 was associated with lymphnode metastases in univariate analyses (one-way ANOVA) as well as in multivariate analysis (binary logistic regression) (Bcl-2 p=0.003 univariate, p=0.01 multivariate, Bax p=0.05 univariate, p=0.03 multivariate). Bcl-2 overexpression showed an inverse association with cyclin A (p=0.05), while expression of Bcl-xL showed an association only with cyclin D3 (p=0.04). Bcl-xL expression also showed a highly significant association with oestrogen receptor status (p=0.009). Bcl-2 and Bcl-xL showed an association with different D-type cyclins, indicating different pathways of pathogenesis. Expression of Bcl-2 was associated with better patient survival in univariate analysis (Kaplan meyer p=0.04), but lost its prognostic value in multivariate analysis (Cox regression p=0.2).  相似文献   
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