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61.
miR‐203 inhibits augmented proliferation and metastasis of hepatocellular carcinoma residual in the promoted regenerating liver 下载免费PDF全文
Xiao‐Bo Zheng Xiao‐Bo Chen Liang‐Liang Xu Ming Zhang Lei Feng Peng‐Sheng Yi Jian‐Wei Tang Ming‐Qing Xu 《Cancer science》2017,108(3):338-346
Liver resection is still the most commonly used therapeutic treatment for hepatocellular carcinoma (HCC), and liver regeneration promotes HCC growth in the regenerating liver. The high recurrence/metastasis of HCC is the main cause of death for HCC patients after liver resection. However, how the augmented growth and metastasis of residual HCC induced by the promoted liver regeneration following liver resection can be abolished remains unclear. In this study, a rat model with liver cirrhosis and diffused HCC was established by administration of diethylnitrosamine. Recombinant miR‐203 adenovirus was administered to induce hepatic miR‐203 overexpression and 30% partial hepatectomy (PH) followed. The effect of miR‐203 on the proliferation, invasion and metastasis of the residual HCC in the remnant cirrhotic liver with promoted regeneration was investigated. We found that the basic spontaneous regeneration of the non‐tumorous liver by 30% PH promoted proliferation, invasion and lung metastasis of the hepatic residual HCC. miR‐203 overexpression further promoted the regeneration of the non‐tumorous liver by upregulating Ki67 expression and enhancing IL‐6/SOCS3/STAT3 pro‐proliferative signals. Importantly, miR‐203 overexpression markedly inhibited the proliferation, invasion and metastasis of hepatic residual HCC through suppressing expression of Ki67, CAPNS1 and lung metastasis. Moreover, it was found that miR‐203 overexpression reversed the epithelial–mesenchymal transition induced by hepatectomy through targeting IL‐1β, Snail1 and Twist1. In conclusion, our results suggested that miR‐203 overexpression inhibited the augmented proliferation and lung metastasis of the residual HCC induced by the promoted liver regeneration following PH partly by regulating epithelial–mesenchymal transition. 相似文献
62.
耐药结核病的涌现,使发展新型抗耐药结核药物变得尤为迫切。本研究选择生长快且无致病性的耻垢分枝杆菌为研究对象,探索快速评价药物抗异烟肼耐药结核分枝杆菌的能力。inhA是异烟肼的作用靶点,由于inhA的突变或者过表达可以引起结核分枝杆菌对异烟肼耐药性的产生。通过将inhA克隆入pMV261中,构建过表达inhA的耻垢分枝杆菌。结果显示,过量表达inhA的耻垢分枝杆菌对异烟肼的敏感性下降了100倍以上。建立了利用刃天青为指示剂的抗异烟肼耐药株的快速药效评价方法,可快速对药物的活性进行定性或定量评价,为进行新型抗结核药物的高通量筛选和药效评价奠定基础。 相似文献
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Mengya Tong Mingzhao Gao Yongping Xu Li Fu Yun Li Xubin Bao Haoyu Fu Haitian Quan Liguang Lou 《Cancer science》2019,110(11):3584-3594
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) have been used as the first‐line treatment of non‐small cell lung cancers (NSCLC) harboring EGFR‐activating mutations, but acquired resistance is ubiquitous and needs to be solved urgently. Here, we introduce an effective approach for overcoming resistance to the EGFR‐TKI, AZD9291, in NSCLC cells using SHR‐A1403, a novel c‐mesenchymal‐epithelial transition factor (c‐Met)‐targeting antibody‐drug conjugate (ADC) consisting of an anti‐c‐Met monoclonal antibody (c‐Met mAb) conjugated to a microtubule inhibitor. Resistant cells were established by exposing HCC827 to increasing concentrations of EGFR‐TKI. c‐Met was found to be overexpressed in most resistant cells. AZD9291 resistance was partially restored by combination of AZD9291 and crizotinib only in resistant cells overexpressing phospho‐c‐Met, which synergistically inhibited c‐Met‐mediated phosphorylation of the downstream targets ERK1/2 and AKT. In resistant cells overexpressing c‐Met, neither crizotinib nor c‐Met mAb was able to overcome AZD9291 resistance. In contrast, SHR‐A1403 strongly inhibited proliferation of AZD9291‐resistant HCC827 overexpressing c‐Met, regardless of the levels of c‐Met phosphorylation. SHR‐A1403 bound to resistant cells overexpressing c‐Met was internalized into cells and released associated microtubule inhibitor, resulting in cell‐killing activity that was dependent on c‐Met expression levels only, irrespective of the involvement of c‐Met or EGFR signaling in AZD9291 resistance. Consistent with its activity in vitro, SHR‐A1403 significantly inhibited the growth of AZD9291‐resistant HCC827 tumors and caused tumor regression in vivo. Thus, our findings show that SHR‐A1403 efficiently overcomes AZD9291 resistance in cells overexpressing c‐Met, and further indicate that c‐Met expression level is a biomarker predictive of SHR‐A1403 efficacy. 相似文献
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67.
FoxM1是Forkhead Box( Fox)转录因子家族的成员之一。近年来研究发现,FoxM1在脑胶质瘤的发生和发展中起着重要的作用。研究表明,人脑胶质瘤组织中FoxM1的表达明显高于正常脑组织,并且其表达水平与胶质瘤等级相关。同时,FoxM1信号途径参与调节细胞分化、增殖、凋亡、血管生成及维持干细胞自我更新等生理过程,并与多种致瘤信号途径有关。通过下调FoxM1的表达,可以抑制胶质瘤细胞的增殖、分化等生物学行为。因此,FoxM1的靶向治疗将为胶质瘤药物研发治疗提供一个潜在的新的作用靶点。 相似文献
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69.
Expression of MDR1/P-glycoprotein,the multidrug resistance protein MRP,and the lung-resistance protein LRP in multiple myeloma 总被引:7,自引:0,他引:7
Schwarzenbach H 《Medical oncology (Northwood, London, England)》2002,19(2):87-104
The purpose of this study was to determine the incidence of three genes associated with multidrug resistance (MDR) in multiple
myeloma in relation to treatment status. MDR1/Pgp (P-glycoprotein) expression was detected in 41% of 93 myeloma samples. Generally,
the incidence of MDR1/Pgp expression was higher in pretreated samples, and treatments with doxorubicin and/or vincristine
were more effective in MDR1/Pgp expression than with alkylating agents. A significant association was observed between MDR1/Pgp-positiveness
and the ability of verapmil to increase doxorubicin sensitivity, suggesting functional relevance of MDR1/Pgp expression. MRP
(multidrug resistance protein) expression was detected in 20.5% of 88 myeloma samples, in 26% at the mRNA level analyzed by
quantitative reverse transriptase-polymerase chain reaction, and in only 3 of 79 samples by immunohistochemistry. LRP (lung-resistance
protein) protein expression was observed in 12.5% of 72 myeloma samples. MRP and LRP expression was similar in samples with
and without prior therapy. Approximately 80% of the myeloma samples with detectable mRNA expression of MDR1 and MRP exhibited
low expression levels corresponding to <10% of the Pgp- and MRP-overexpressing multidrug-resistant human myeloma cell lines
8226/Dox6 and 8226/DOXint40c, respectively. Some normal bone marrow samples showed higher levels of MRP mRNA as compared to
myeloma specimens, whereas MDR1 mRNA expression in normal bone marrow was much lower (≤ 5%) than that in 8226/Dox6. These
findings indicate a requirement to develop single-cell assays for MRP detection in multiple myeloma that are more sensitive
than immunohistochemistry and might be useful to evaluate the incidence of genes associated with MDR. 相似文献
70.
Comparison of p53 expression in proximal and distal gastric cancer: Histopathologic correlation and prognostic significance 总被引:2,自引:0,他引:2
Huihuan Tang MD Shuichi Hokita MD PhD Xiangming Che MD Masamichi Baba MD PhD Kuniaki Aridome MD PhD Fumio Kijima MD Gen Tanabe MD PhD Sonshin Takao MD PhD Dr. Takashi Aikou MD PhD 《Annals of surgical oncology》1997,4(6):470-474
Background: The overexpression of p53 has been found to be correlated with prognosis of some carcinomas, including gastric cancer, but
no studies have reported on its relationship to the location of gastric cancer. In the present study, we compared the p53
expression of proximal and distal gastric cancer concerning histopathology and prognosis.
Methods: A total of 170 tumors in the patients with proximal (80 cases) and distal (90 cases) gastric cancer were studied by immunohistochemical
methods.
Results: p53 immunopositivity was detected in 28.8% of all tumors. The p53-positive expression in proximal gastric cancer was higher
than in distal gastric cancer (38.8% vs. 20.0%, p<0.05). A 5-year survival analysis showed that there is no significant difference
between tumors that are p53 positive and p53 negative. No correlation was found between p53 expression and histopathology
of gastric cancer.
Conclusion: p53 nuclear staining is not useful as a prognostic indicator or as a parameter in gastric cancer. 相似文献