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BackgroundMolecular markers can help identify patients with early-stage non–small-cell lung cancer (NSCLC) with a high risk of relapse. Excision repair cross-complementing 1 (ERCC1), Xeroderma pigmentosum group G (XPG), and breast cancer 1 (BRCA1) are involved in DNA damage repair, whereas ribonucleotide reductase M1 (RRM1) is implicated in DNA synthesis. Expression levels of these molecules might therefore have a prognostic role in lung cancer.Patients and MethodsWe examined ERCC1, RRM1, XPG, and BRCA1 mRNA levels by real-time quantitative polymerase chain reaction in 54 patients with stage IB-IIB resected NSCLC. A strong correlation was observed between the 4 genes.ResultsFor patients with low BRCA1, regardless of XPG mRNA expression levels, disease-free survival (DFS) was not reached. For patients with intermediate/high BRCA1 and high XPG, DFS was 50.7 months. However, for patients with intermediate/high BRCA1 and low/intermediate XPG, DFS decreased to 16.3 months (P = .002). Similar differences were observed in overall survival, with median survival not reached for patients with low BRCA1, regardless of XPG levels, or for patients with intermediate/high BRCA1 and high XPG. Conversely, for patients with intermediate/high BRCA1 levels and low/intermediate XPG levels, median survival dropped to 25.5 months (P = .007).ConclusionBRCA1 and XPG were identified as independent prognostic factors for both median survival and DFS. High BRCA1 mRNA expression confers poor prognosis in early NSCLC, and the combination of high BRCA1 and low XPG expression still further increases the risk of shorter survival. These findings can help optimize the customization of adjuvant chemotherapy.  相似文献   
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To improve the knowledge of the underlying mechanisms of action involved in air pollution Particulate Matter (PM)-induced toxicity in human lungs, with a particular interest of the crucial role played by coated-organic chemicals, we were interested in the metabolic activation of Polycyclic Aromatic Hydrocarbons (PAH)-coated onto air pollution PM, and, thereafter, the formation of PAH-DNA adducts in a human lung epithelial cell model (A549 cell line). Cells were exposed to Dunkerque city's PM(2.5) at its Lethal Concentrations at 10% and 50% (i.e. LC(10)=23.72 microg/mL or 6.33 microg/cm2, and LC(50)=118.60 microg/mL or 31.63 microg/cm2), and the study of Cytochrome P450 (CYP) 1A1 gene expression (i.e. RT-PCR) and protein activity (i.e. EROD activity), and the formation of PAH-DNA adducts (i.e. 32P-postlabeling), were investigated after 24, 48, and/or 72 h. PAH, PolyChlorinated Dibenzo-p-Dioxins and -Furans (PCDD/F), Dioxin-Like PolyChlorinated Biphenyls (DLPCB), and PolyChlorinated Biphenyls (PCB)-coated onto collected PM were determined (i.e. GC/MS and HRGC/HRMS, respectively), Negative (i.e. TiO2 or desorbed PM, dPM; EqLC10=19.42 microg/mL or 5.18 microg/cm2, and EqLC50=97.13 microg/mL or 25.90 microg/cm2), and positive (i.e. benzo(a)pyrene; 1 microM) controls were included in the experimental design. Statistically significant increases of CYP1A1 gene expression and protein activity were observed in A549 cells, 24, 48 and 72 h after their exposure to dPM, suggesting thereby that the employed outgassing method was not efficient enough to remove total PAH. Both the CYP1A1 gene expression and EROD activity were highly induced 24, 48 and 72 h after cell exposure to PM. However, only very low levels of PAH-DNA adducts, also not reliably quantifiable, were reported 72 h after cell exposure to dPM, and, particularly, PM. The relatively low levels of PAH together with the presence of PCDD/F, DLPCB, and PCB-coated onto Dunkerque City's PM 2.5 could notably contribute to explain the borderline detection of PAH-DNA adducts in dPM and/or PM-exposed A549 cells. Hence, remaining very low doses of PAH in dPM or relatively low doses of PAH-coated onto PM were involved in enzymatic induction, a key feature in PAH-toxicity, but failed to show a clear genotoxicity in this in vitro study. We also concluded that, in the human lung epithelial cell model we used, and in the experimental conditions we chose, bulky-DNA adduct formation was apparently not a major factor involved in the Dunkerque City's PM 2.5-induced toxicity.  相似文献   
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The granular cell tumor or Abrikossoff''s tumor is a rare tumor, most often benign in evolution. Malignant forms are exceptional. We report, here, a very rare case of granular cell tumor, localized in the perianal region, in a 54-year-old woman with lung metastases. CT and MRI with contrast showed a locally advanced tumor process in the right para-anal region associated with multiple "balloon release" lung lesions. The diagnosis was confirmed by immunostaining after surgical biopsy. Very few cases of malignant granular cell tumors with lung metastasis have been reported in the literature.  相似文献   
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Many complications are known to occur in association with a diaphragmatic hernia. Acute pancreatitis occurring in this situation is very rare. In this paper, we report a case and describe the radiographic features of this complication. We report an unusual case of acute pancreatitis complicating a neglected post-traumatic diaphragmatic hernia in a 30-year-old male. This patient had a history of an abdominal trauma 5 years ago, and arrived at the emergency room with epigastria and left chest pain and vomiting. Serum lipase was elevated. Acute pancreatitis could be considered as an exceptional complication of diaphragmatic hernia. It is a serious diagnostic and therapeutic challenge. The fundamental roles of CT are to determine the diaphragmatic defect, the abdominal content involving, the Balthazar scoring of pancreatitis, and the presence of local complications. Even if a conservative approach is preferred when facing a diagnosis of pancreatitis, timing of surgery should be carefully considered.  相似文献   
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The removal of Ni(II), Cu(II) and Zn(II) from aqueous model solutions and real wastewater samples by using pod razor (Ensis siliqua) shell powder has been investigated under several conditions such as heavy metal concentrations, pH, contact time, powder dosage. It was found that the removal of heavy metals was dependent on the dose of the biomineral and contact time. The results showed that this low-cost material can be fruitfully used for the removal of heavy metal ions such as Ni(II), Cu(II) and Zn(II) below concentration of 200 mg/L applying a shell powder dose of 1.2–4 g/L. The minimal dose for removal of Cu(II) and Zn(II) from industrial wastewater was found to be 1.2 g/L, while for Ni this value amounted to 1.6 g/L. The contact time necessary for quantitative removal was found to be 30–60 min and the optimum initial pH range was between 4 and 5.  相似文献   
50.

Introduction

Partner and localizer of BRCA2 (PALB2) is essential for homologous recombination repair. We examined mRNA levels of DNA repair genes, including partner and localizer of BRCA2 gene (PALB2), ring finger protein 8 gene (RNF8), replication timing regulatory factor 1 gene (RIF1), ATM serine/threonine kinase gene (ATM), and tumor protein p53 binding protein 1 gene (53BP1) as predictive biomarkers for cisplatin-docetaxel in the European phase III BRCA1, DNA repair associated (BRCA1)receptor-associated protein 80 (RAP80) expression customization (BREC) phase III clinical trial (ClinicalTrials.gov identifier NCT00617656).

Methods

The study was a prespecified secondary objective of the BREC trial. We assessed mRNA levels of PALB2 and four more DNA repair genes (RNF8, RIF1, ATM and 53BP1) as biomarkers in tissue from 177 patients with cisplatin-docetaxel–treated NSCLC. We examined the relationship of gene expression levels with progression-free survival, overall survival, and response.

Results

In 177 patients with NSCLC (who had a median age of 62 years and included 140 men and 91 patients with adenocarcinoma), only high PALB2 mRNA expression was predictive in the progression-free survival Cox regression analysis (hazard ratio = 0.63, 95% confidence interval: 0.42–0.83, p = 0.0080). PALB2 was also predictive of overall survival (hazard ratio = 0.68, 95% confidence interval: 0.42–0.90, p = 0.0266). Among the 158 patients evaluable for response, high PALB2 mRNA expression was predictive of response to cisplatin-docetaxel. Specifically, an objective response rate of 77% to cisplatin-docetaxel was observed for patients with high PALB2 mRNA expression compared with a rate of only 23 % for those with low PALB2 mRNA expression (p = 0.0448).

Conclusions

High PALB2 mRNA expression identified patients with NSCLC who significantly benefited from cisplatin-docetaxel chemotherapy in the European BREC phase III clinical trial. The combination of chemotherapy with immunotherapy will become the standard of care, and a predictive marker of response to chemotherapy may accurately guide therapeutic decision making.  相似文献   
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