全文获取类型
收费全文 | 238篇 |
免费 | 0篇 |
国内免费 | 9篇 |
专业分类
耳鼻咽喉 | 2篇 |
儿科学 | 6篇 |
妇产科学 | 3篇 |
基础医学 | 20篇 |
临床医学 | 29篇 |
内科学 | 46篇 |
神经病学 | 25篇 |
特种医学 | 10篇 |
外科学 | 41篇 |
综合类 | 5篇 |
预防医学 | 10篇 |
药学 | 11篇 |
中国医学 | 1篇 |
肿瘤学 | 38篇 |
出版年
2023年 | 1篇 |
2022年 | 6篇 |
2021年 | 12篇 |
2020年 | 2篇 |
2019年 | 6篇 |
2018年 | 6篇 |
2017年 | 2篇 |
2016年 | 12篇 |
2015年 | 5篇 |
2014年 | 5篇 |
2013年 | 18篇 |
2012年 | 28篇 |
2011年 | 37篇 |
2010年 | 19篇 |
2009年 | 16篇 |
2008年 | 18篇 |
2007年 | 11篇 |
2006年 | 21篇 |
2005年 | 11篇 |
2004年 | 4篇 |
2003年 | 5篇 |
2002年 | 2篇 |
排序方式: 共有247条查询结果,搜索用时 109 毫秒
1.
Feng-Yuan Liu Chien-Yu Lin Joseph T Chang Shu-Hang Ng Shy-Chyi Chin Hung-Ming Wang Chun-Ta Liao Sheng-Chieh Chan Tzu-Chen Yen 《Journal of nuclear medicine》2007,48(10):1614-1619
Conventional work-up (CWU) with chest radiography, abdominal ultrasonography, and skeletal scintigraphy has limited value in M staging of nonkeratinizing nasopharyngeal carcinoma (NPC). Our aim was to evaluate whether (18)F-FDG PET could replace CWU by comparing their diagnostic efficacies. METHODS: Patients with histologically proven nonkeratinizing NPC and no prior treatment were prospectively enrolled. All study participants underwent CWU and (18)F-FDG PET for primary M staging. Distant metastasis was considered to be present if there was any reliable evidence identified within 1 y after diagnosis. The comparative diagnostic efficacies of (18)F-FDG PET, CWU, and the combination of (18)F-FDG PET and CWU (PET+CWU) were evaluated using the areas under the receiver-operating-characteristic (ROC) curves. RESULTS: Sixty-one (20.3%) of 300 eligible patients were found to have distant metastases. On a patient-based analysis, (18)F-FDG PET was found to be more effective than CWU (P < 0.001), whereas it was equally effective with PET+CWU (P = 0.130). On region-based analyses, (18)F-FDG PET was more effective than skeletal scintigraphy and chest radiography for detecting bone metastases (P < 0.001) and chest metastases (P < 0.001), respectively. (18)F-FDG PET and abdominal ultrasound were equally effective for detecting hepatic metastases (P = 0.127). On region-based analyses, the combination of (18)F-FDG PET and CWU did not yield any noticeable increase in diagnostic efficacy. CONCLUSION: (18)F-FDG PET can replace CWU in primary M staging of nonkeratinizing NPC. 相似文献
2.
Chu Yu-Ju Jeng Wen-Juei Pan Mei-Hung Hu Hui-Han Luo Wen-Sheng Su Chien-Yu Chiang Chen-Tse Jen Chin-Lan Chen Chien-Jen Yang Hwai-I 《Journal of gastroenterology》2022,57(6):423-432
Journal of Gastroenterology - In chronic hepatitis B virus (HBV) infection, earlier seroclearance of hepatitis B e antigen (HBeAg) is associated with more favorable outcomes. Soluble programmed... 相似文献
3.
Hui-Ju Yang Pin-Chun Chen Chien-Ting Huang Tzu-Lin Cheng Sheng-Ping Hsu Chien-Yu Chen Juu-Chin Lu Chih-Tien Wang 《The Journal of neuroscience》2021,41(13):2828
Common fusion machinery mediates the Ca2+-dependent exocytosis of synaptic vesicles (SVs) and dense-core vesicles (DCVs). Previously, Synapsin Ia (Syn Ia) was found to localize to SVs, essential for mobilizing SVs to the plasma membrane through phosphorylation. However, whether (or how) the phosphoprotein Syn Ia plays a role in regulating DCV exocytosis remains unknown. To answer these questions, we measured the dynamics of DCV exocytosis by using single-vesicle amperometry in PC12 cells (derived from the pheochromocytoma of rats of unknown sex) overexpressing wild-type or phosphodeficient Syn Ia. We found that overexpression of phosphodeficient Syn Ia decreased the DCV secretion rate, specifically via residues previously shown to undergo calmodulin-dependent kinase (CaMK)-mediated phosphorylation (S9, S566, and S603). Moreover, the fusion pore kinetics during DCV exocytosis were found to be differentially regulated by Syn Ia and two phosphodeficient Syn Ia mutants (Syn Ia-S62A and Syn Ia-S9,566,603A). Kinetic analysis suggested that Syn Ia may regulate the closure and dilation of DCV fusion pores via these sites, implying the potential interactions of Syn Ia with certain DCV proteins involved in the regulation of fusion pore dynamics. Furthermore, we predicted the interaction of Syn Ia with several DCV proteins, including Synaptophysin (Syp) and soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins. By immunoprecipitation, we found that Syn Ia interacted with Syp via phosphorylation. Moreover, a proximity ligation assay (PLA) confirmed their phosphorylation-dependent, in situ interaction on DCVs. Together, these findings reveal a phosphorylation-mediated regulation of DCV exocytosis by Syn Ia.SIGNIFICANCE STATEMENT Although they exhibit distinct exocytosis dynamics upon stimulation, synaptic vesicles (SVs) and dense-core vesicles (DCVs) may undergo co-release in neurons and neuroendocrine cells through an undefined molecular mechanism. Synapsin Ia (Syn Ia) is known to recruit SVs to the plasma membrane via phosphorylation. Here, we examined whether Syn Ia also affects the dynamics of DCV exocytosis. We showed that Syn Ia regulates the DCV secretion rate and fusion pore kinetics during DCV exocytosis. Moreover, Syn Ia-mediated regulation of DCV exocytosis depends on phosphorylation. We further found that Syn Ia interacts with Synaptophysin (Syp) on DCVs in a phosphorylation-dependent manner. Thus, these results suggest that Syn Ia may regulate the release of DCVs via phosphorylation. 相似文献
4.
5.
Leptospirosis is a zoonotic disease with protean manifestations. A 35-year-old male presented with pneumonia after the Typhoon Morakot. Skin rash, conjunctival suffusion, and subconjunctival hemorrhage led us to the diagnosis of leptospirosis and the microscopic agglutination test confirmed the diagnosis. This patient well demonstrated the picture of conjunctival suffusion and reminded us of the alertness of leptospirosis after a typhoon. 相似文献
6.
Jen-Chung Ko Hsien-Chun Chiu Jhan-Jhang Syu Yi-Jun Jian Chien-Yu Chen Yun-Ting Jian Yi-Jhen Huang Ting-Yu Wo Yun-Wei Lin 《Biochemical pharmacology》2014
Tamoxifen is a triphenylethylene nonsteroidal estrogen receptor (ER) antagonist used worldwide as an adjuvant hormone therapeutic agent in the treatment of breast cancer. However, the molecular mechanism of tamoxifen-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Thymidine phosphorylase (TP) is an enzyme of the pyrimidine salvage pathway which is upregulated in cancers. In this study, tamoxifen treatment inhibited cell survival in two NSCLC cells, H520 and H1975. Treatment with tamoxifen decreased TP mRNA and protein levels through AKT inactivation. Furthermore, expression of constitutively active AKT (AKT-CA) vectors significantly rescued the decreased TP protein and mRNA levels in tamoxifen-treated NSCLC cells. In contrast, combination treatment with PI3K inhibitors (LY294002 or wortmannin) and tamoxifen further decreased the TP expression and cell viability of NSCLC cells. Knocking down TP expression by transfection with small interfering RNA of TP enhanced the cytotoxicity and cell growth inhibition of tamoxifen. Erlotinib (Tarceva, OSI-774), an orally available small molecular inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, is approved for clinical treatment of NSCLC. Compared to a single agent alone, tamoxifen combined with erlotinib resulted in cytotoxicity and cell growth inhibition synergistically in NSCLC cells, accompanied with reduced activation of phospho-AKT and phospho-ERK1/2, and reduced TP protein levels. These findings may have implications for the rational design of future drug regimens incorporating tamoxifen and erlotinib for the treatment of NSCLC. 相似文献
7.
Chao-Hung Kuo Chung-Jung Liu Chien-Yu Lu Huang-Ming Hu Fu-Chen Kuo Yu-Sen Liou Yuan-Chieh Yang Ming-Chia Hsieh Oscar K. Lee Deng-Chyang Wu Sophie S.W. Wang Yao-Li Chen 《International journal of medical sciences》2014,11(1):7-16
Gender differences in terms of mortality among many solid organ malignancies have been proved by epidemiological data. Estrogen has been suspected to cast a protective effect against cancer because of the lower mortality of gastric cancer in females and the benefits of hormone replacement therapy (HRT) in gastric cancer. Hence, it suggests that 17β-estradiol (E2) may affect the behavior of cancer cells. One of the key features of cancer-related mortality is metastasis. Accumulating evidences suggest that human bone marrow mesenchymal stem cells (HBMMSCs) and its secreted CCL-5 have a role in enhancing the metastatic potential of breast cancer cells. However, it is not clear whether E2 would affect HBMMSCs-induced mobility in gastric cancer cells. In this report, we show that CCL-5 secreted by HBMMSCs enhanced mobility in human AGS gastric cancer cells via activation of Src/Cas/Paxillin signaling pathway. Treatment with specific neutralizing antibody of CCL-5 significantly inhibited HBMMSCs-enhanced mobility in human AGS gastric cancer cells. We further observe that 17β-estradiol suppressed HBMMSCs-enhanced mobility by down-regulating CCL5-Src/Cas/paxillin signaling pathway in AGS cells. Collectively, these results suggest that 17β-estradiol treatment significantly inhibits HBMMSCS-induced mobility in human AGS gastric cancer cells. 相似文献
8.
Chang-Ching Weng Chien-Yu Chao She-Ting Wu Ping-Hsien Tsou Wei-Tin Chen Bor-Ran Li Yaw-Kuen Li 《RSC advances》2021,11(46):28551
Enzyme-linked immunosorbent assays (ELISAs) are tests that uses antibody recognition and enzyme catalytic activity to identify a substance, and they have been widely used as a diagnostic tool in the clinic. However, performing an ELISA requires various liquid handling steps and long binding times. To solve this problem, we developed a magnetic microfluidic ELISA system (MMF-ELISA). Integration with nickel magnetic nanoparticles can streamline the ELISA process in a fully automated manner for Streptococcus pneumoniae detection. First, we synthesized paramagnetic surface-oxidized nickel nanoparticles (Ni/NiO NPs) to carry protein G. Then, we assembled a SUM290 (UlaG)-specific antibody on protein G. Finally, we integrated the NPs on a microfluidics chip for S. pneumoniae detection. The chip contains three different layers to trap the solutions; the bottom layer SiO2 is patterned on hydrophobic polymers and integrated with the middle layer PDMS and the top layer PMMA. With Arduino and motor IC, we developed an automated platform for S. pneumoniae detection. Microfluidic ELISAs can reduce the manual handling and operation time. Furthermore, the developed system can be extended to multiple areas for ELISA-related assays. This economical, rapid and portable system may become a promising platform for sensing S. pneumoniae in clinical applications.Enzyme-linked immunosorbent assays (ELISAs) are tests that uses antibody recognition and enzyme catalytic activity to identify a substance, and they have been widely used as a diagnostic tool in the clinic. 相似文献
9.
10.
Concomitant intramyocardial and epicardial vasculitis in an autopsied heart allograft for cardiac rhabdomyosarcoma 总被引:1,自引:0,他引:1
Primary cardiac tumours are rare, with only one quarter of the patients being malignant. The vast majority of malignant neoplasms of the heart are sarcomas. We describe a patient of primary cardiac rhabdomyosarcoma presented as coronary artery disease and recurrent myocardial infarction. Histopathologic finding of the excised native heart revealed a high grade pleomorphic rhabdomyosarcoma in the myoepicardial portion of the anterior wall with rupture. The accompanying unusual feature was myocardial infarction because of tumour emboli of the left anterior descending and left circumflex coronary arteries. After transplantation, the patient developed mild to moderate acute cellular rejection of the transplanted heart on post-transplantation day 1, 8, and 44, respectively. Unfortunately, he expired on the post-transplantation day 47 because of acute rejection, presenting as concomitant intramyocardial and epicardial lymphocytic vasculitis and multifocal myocardial ischaemia. We found that this uncommon medial lymphocytic vasculitis lesion was mediated by T cells and also by antibody directly against smooth muscle cells of small arteries. The consequence of such immune response would be compromised myocardial oxygenation resulting in allograft failure. 相似文献