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71.
Background
An increasing amount of evidence has revealed that microRNAs regulate various biological processes, including cell differentiation, cell proliferation, apoptosis, drug resistance, and fat metabolism. Studies have shown that miR-93’s targetome in cancer has not been fully defined. Moreover, the role of miR-93 in epithelial ovarian carcinoma (EOC) remains largely unknown.Methods
MIR-93 mRNA expression in normal ovarian tissue, benign tumors, borderline tumors, primary ovarian carcinomas, and metastatic omentum was quantified. The ovarian carcinoma cell lines OVCAR3, SKOV3/DDP, and HO8910-PM were transfected with miR-93-5P, after which cell phenotype and expression of relevant molecules were assayed. Dual-luciferase reporter assay and a xenograft mouse model were used to examine miR-93 and its target gene RHOC (Ras homolog gene family member C).Results
MIR-93 mRNA expression was significantly lower in ovarian carcinomas and borderline tumors than in normal ovarian tissues (p < 0.05), and was lower in metastatic omentum than in relative primary ovarian carcinomas (p < 0.05). MIR-93 mRNA expression was also negatively associated with differentiation (well vs. poor and moderate) and International Federation of Gynecology and Obstetrics staging (FIGO stage I/II vs. stage III/IV) in ovarian carcinoma (p < 0.05), besides, miR-93 was higher expressed in mucinous adenocarcinoma than the other types (p < 0.05). MiR-93-5P overexpression reduced proliferation (p < 0.05); promoted G1 or S arrest and apoptosis (p < 0.05); suppressed migration and invasion (p < 0.05); and reduced RhoC, P70S6 kinase, Bcl-xL, matrix metalloproteinase 9 (MMP9) mRNA or protein expression; conversely, it induced P53 and cleaved PARP expression (p < 0.05). Dual-luciferase reporter assay indicated that miR-93 directly targeted RhoC by binding its 3′ untranslated region. MiR-93-5P transfection also suppressed tumor development and RhoC expression (determined by immunohistochemistry) in vivo in the xenograft mouse model (p < 0.05).Conclusions
This is the first demonstration that miR-93-5P may inhibit EOC tumorigenesis and progression by targeting RhoC. These findings indicate that miR-93-5P is a potential suppressor of ovarian cellular proliferation. The involvement of miR-93-5P–mediated RhoC downregulation in inhibiting EOC aggressiveness may provide extended insight into the molecular mechanisms underlying cancer aggressiveness. 相似文献72.
Colorectal cancer (CRC) is one of the most common malignancies worldwide. The prognosis for this cancer is poor, and the development of novel biomarkers, particularly non-invasive surrogate biomarkers, is urgently needed. Recent studies have demonstrated that microRNAs (miRNAs) are stably detectable in the blood and can serve as useful biomarkers for various types of cancer. In this study, the miR-183 expression levels were found to be significantly overexpressed in plasma samples from CRC patients compared with controls, and the postoperative plasma miR-183 levels were significantly reduced compared with the preoperative levels. The value of the area under the receiver operating characteristic (ROC) curve obtained for miR-183 was 0.829, which was higher than those for carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). High plasma miR-183 expression was significantly associated with lymph node metastasis, distant metastasis, higher pTNM stage (III-IV), and tumor recurrence. CRC patients with elevated miR-183 expression in plasma displayed shorter disease-free survival (DFS) and lower overall survival (OS). More importantly, plasma miR-183 was independently correlated with tumor recurrence and a lower OS. Collectively, our results suggested that the elevated miR-183 in the plasma could be a promising biomarker for predicting the risk of tumor recurrence and poor survival in CRC patients. 相似文献
73.
Malignant risk stratification of thyroid FNA specimens with indeterminate cytology based on molecular testing 下载免费PDF全文
74.
Jia Ke Zhiju Zhao Su-Hyung Hong Shoumin Bai Zhen He Fayaz Malik Jiahui Xu Lei Zhou Weilong Chen Rachel Martin-Trevino Xiaojian Wu Ping Lan Yongju Yi Christophe Ginestier Ingrid Ibarra Li Shang Sean McDermott Tahra Luther Shawn G. Clouthier Max S. Wicha Suling Liu 《Oncotarget》2015,6(6):3709-3721
Increasing evidence suggests that lineage specific subpopulations and stem-like cells exist in normal and malignant breast tissues. Epigenetic mechanisms maintaining this hierarchical homeostasis remain to be investigated. In this study, we found the level of microRNA221 (miR-221) was higher in stem-like and myoepithelial cells than in luminal cells isolated from normal and malignant breast tissue. In normal breast cells, over-expression of miR-221 generated more myoepithelial cells whereas knock-down of miR-221 increased luminal cells. Over-expression of miR-221 stimulated stem-like cells in luminal type of cancer and the miR-221 level was correlated with clinical outcome in breast cancer patients. Epithelial-mesenchymal transition (EMT) was induced by overexpression of miR-221 in normal and breast cancer cells. The EMT related gene ATXN1 was found to be a miR-221 target gene regulating breast cell hierarchy. In conclusion, we propose that miR-221 contributes to lineage homeostasis of normal and malignant breast epithelium. 相似文献
75.
Xiaoping Liu Qianqian Lei Zhibin Yu Gang Xu Hailin Tang Wei Wang Zeyou Wang Guiyuan Li Minghua Wu 《Oncotarget》2015,6(10):7930-7943
LIM-only protein 3 (LMO3), a member of the LIM-only protein group, is a new DNA methylation gene that was identified in gliomas via the MeDIP-Chip in our previous study. In this study, we found that LIM-only protein 3 (LMO3) is hypomethylated and overexpressed in glioma cells and tissues. The overexpression of LMO3 was correlated with a poor prognosis in glioma patients, and LMO3 was indirectly inhibited by the tumor suppressor miR-101, which is a potential prognosis marker of gliomas. MiR-101 decreased the expression of LMO3 by reversing the methylation status of the LMO3 promoter and by inhibiting the presence of the methylation-related histones H3K4me2 and H3K27me3 and increasing the presence of H3K9me3 and H4K20me3 on the promoter. It was determined that miR-101 decreases the occupancy of H3K27me3 by inhibiting EZH2, DNMT3A and EED and decreases the H3K9me3 occupancy on the LMO3 promoter via SUV39H1, SUV39H2, G9a and PHF8. Furthermore, miR-101 suppresses the expression of LMO3 by decreasing USF and MZF1. 相似文献
76.
Qinhong Xu Pei Li Xin Chen Liang Zong Zhengdong Jiang Ligang Nan Jianjun Lei Wanxing Duan Dong Zhang Xuqi Li Huanchen Sha Zheng Wu Qingyong Ma Zheng Wang 《Oncotarget》2015,6(16):14153-14164
MicroRNAs are involved in the initiation and progression of pancreatic cancer. In this study, we showed that miR-221/222 is overexpressed in pancreatic cancer. MiR-221/222 overexpression significantly promoted pancreatic cancer cell proliferation and invasion while inhibiting apoptosis. The expression of the matrix metalloproteinases (MMPs) MMP-2 and MMP-9 was increased in miR-221/222 mimic-transfected pancreatic cancer cells. Validation experiments identified TIMP-2 as a direct target of miR-221/222. These data indicate that overexpressed miR-221/222 may play an oncogenic role in pancreatic cancer by inducing the expression of MMP-2 and MMP-9, thus leading to cancer cell invasion. 相似文献
77.
Valentinus T. Valdimarsson Ingvar Syk Gert Lindell Agneta Norén Bengt Isaksson Per Sandström Magnus Rizell Bjarne Ardnor Christian Sturesson 《HPB : the official journal of the International Hepato Pancreato Biliary Association》2018,20(5):441-447
Background
Patients with synchronous colorectal liver metastases (sCRLM) are increasingly operated with liver resection before resection of the primary cancer. The aim of this study was to compare outcomes in patients following the liver-first strategy and the classical strategy (resection of the bowel first) using prospectively registered data from two nationwide registries.Methods
Clinical, pathological and survival outcomes were compared between the liver-first strategy and the classical strategy (2008–2015). Overall survival was calculated.Results
A total of 623 patients were identified, of which 246 were treated with the liver-first strategy and 377 with the classical strategy. The median follow-up was 40 months. Patients chosen for the classical strategy more often had T4 primary tumours (23% vs 14%, P = 0.012) and node-positive primaries (70 vs 61%, P = 0.015). The liver-first patients had a higher liver tumour burden score (4.1 (2.5–6.3) vs 3.6 (2.2–5.1), P = 0.003). No difference was seen in five-year overall survival between the groups (54% vs 49%, P = 0.344). A majority (59%) of patients with rectal cancer were treated with the liver-first strategy.Conclusion
The liver-first strategy is currently the dominant strategy for sCRLM in patients with rectal cancer in Sweden. No difference in overall survival was noted between strategies. 相似文献78.
Ye Han Yuting Kuang Xiaofeng Xue Xiaobo Guo Pu Li Xu Wang Xingpo Guo Bin Yuan Qiaoming Zhi Hong Zhao 《Biomedicine & Pharmacotherapy》2014
We previously reported that miR-199a-3p is a newly biomarker for diagnosis and novel prognostic indicator in colorectal cancer. However, the miR-199a-3p regulatory mechanism and its target genes are still unclear. In our present study, we demonstrated miR-199a-3p could directly target 3′-UTR of NLK gene by luciferase reporter assay and western blot analysis. We detected NLK expressions in 92 colorectal cancer cases to evaluate its clinicopathologic characteristics in colorectal cancer. Our results showed that NLK expression was significantly downregulated in cancer tissues than NATs, and NLK low-expression was associated with lymph node metastasis, venous invasion, liver metastasis and the TNM stage (P < 0.05). Moreover, Kaplan–Meier analysis showed that low expression of NLK correlated with a shorter overall survival rates of patients with CRC (P < 0.05). In vitro, we also found that NLK suppressed the biological behaviors of colorectal cancer cells, including the abilities of cell proliferation, clone formation, wound healing, migration and invasion (P < 0.05), while overexpression of NLK increased the apoptotic rate of colorectal cancer cells. All these results suggested that NLK was an identified miR-199a-3p target gene and functioned as a tumor suppressor gene in colorectal cancer. NLK could be a novel direction for developing diagnostic and therapeutic approaches in colorectal cancer. 相似文献
79.
Pancreatic cancer is one of the most common types of cancers in the whole world with a poor prognosis. Finding out how the cancer form and develop is the most important way to cure this cancer. miRNAs, 21–22 nucleotides regulatory small non-coding RNAs, have been found to be critical involved in the growth of pancreatic cancer. In this study, we found that miR-92a was up regulated in three kinds of human pancreatic cancer cell lines. There is a correlation between miR-92a and malignant degree of human pancreatic cancer cell lines. Then we found that miR-92a was essential for promoting cell proliferation in human pancreatic cancer. Inhibition of the function of miR-92a repressed the proliferation of pancreatic cancer cells. Further, we found that miR-92a enhanced the activation of JNK signalling pathway by directly targeting the JNK signalling inhibitor DUSP10. DUSP10 is responsible for miR-92a induced JNK signalling and cell proliferation. Altogether, our study showed a miR-92a/DUSP10/JNK signalling pathway that plays an important role in regulating the proliferation of pancreatic cancer cells. 相似文献
80.
microRNAs, a family of small non-coding RNAs, involve in the pathogenesis of several types of cancers, including laryngeal squamous cell carcinoma (LSCC). MiR-370 is frequently aberrant expressed in various types of human cancer including LSCC. However, the role for miR-370 in LSCC remains elusive. Here, we demonstrate that miR-370 was down-regulated in human LSCC tissues. Furthermore, there was an inverse relationship between Forkhead Box ml (FoxM1), which was up-regulated and miR-370 expression in LSCC tissues. FoxM1 was subsequently predicted by bioinformatics and verified to be a target of miR-370 by Luciferase reporter assay. Restored expression of miR-370 in Hep2 cells significantly inhibited cell proliferation. In conclusion, our results suggest that miR-370 may function as a tumor suppressor in LSCC through downregulation of FoxM1, suggesting that miR-370 could serve as a novel potential maker for LSCC therapy. 相似文献