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1.
PET imaging of oncogene overexpression using 64Cu-vasoactive intestinal peptide (VIP) analog: comparison with 99mTc-VIP analog. 总被引:13,自引:0,他引:13
Mathew L Thakur Mohan R Aruva Jean Gariepy Paul Acton Satish Rattan Shyam Prasad Eric Wickstrom Abass Alavi 《Journal of nuclear medicine》2004,45(8):1381-1389
The purpose of this study was to assess the feasibility of PET imaging of oncogene VPAC1 receptors overexpressed in human breast cancer cells. METHODS: Vasoactive intestinal peptide (VIP) analog (TP3982) was synthesized to harbor a carboxy-terminus lysine (Lys) residue separated from VIP-asparagine (Asn(28)) by 4-aminobutyric acid (Aba) as a spacer. Lys was derivatized with diaminopropionic acid coupled to a pair of dibenzoylthioglycolic acid residues as protecting groups. The analog was labeled with (64)Cu at pH 9 ((64)Cu-TP3982) and (99m)Tc at pH 12 ((99m)Tc-TP3982). (99m)Tc-TP3982 and VIP derivatized with Aba-GAGG and labeled with (99m)Tc ((99m)Tc-TP3654) were used as reference agents. Smooth muscle relaxivity assays performed with each derivative and compared with unaltered VIP(28) demonstrated functional integrity. In vitro stability of (64)Cu-TP3982 was determined by challenging the complex with 100-mol excess of diethylenetriaminepentaacetic acid (DTPA), human serum albumin (HSA), and cysteine. In vivo stability was determined in urine and serum for up to 24 h. The mass of the Cu-TP3982 complex was determined by mass spectrometry. Human T47D breast tumor xenografts were grown in athymic nude mice. Planar scintigraphic imaging was performed at 4 and 24 h after the intravenous administration of (99m)Tc-TP3982 and (99m)Tc-TP3654 and PET imaging was performed using a small animal MOSAIC PET scanner, also at 4 and 24 h after injection of (64)Cu-TP3982. Tissue-distribution studies were also performed. In a separate experiment, receptors were blocked by intravenous injection of authentic VIP(28) 30 min before the administration of (64)Cu-TP3982 and tissue distribution was examined. RESULTS: (64)Cu-TP3982 labeling yields were 98% +/- 1.2% and those for (99m)Tc-TP3982 and (99m)Tc-TP3654 were 98.2% +/- 1.1% and 97% +/- 1.6%, respectively. The biologic activity of both VIP analogs was uncompromised. When (64)Cu-TP3982 was challenged with 100-mol excess of DTPA, HSA, or cysteine, >98% radioactivity remained as (64)Cu-TP3982. In vivo, >98% of (64)Cu circulating in plasma remained as (64)Cu-TP3982. Of the (64)Cu excreted in urine 4, 20, and 24 h after injection, >98%, 89.9% +/- 0.9%, and 85% +/- 3%, respectively, were bound to TP3982. The mass of Cu-TP3982 as determined by surface-enhanced laser desorption/ionization time of flight (SELDI-TOF) was 4,049.7 Da. Four hours after receptor blocking with VIP(28), there was a significant reduction in uptake of all tissues except in the liver. With (64)Cu-TP3982, the 4-h postinjection tumor uptake was 10.8 +/- 2.1 %ID/g versus 0.5 +/- 0.02 %ID/g and 0.24 +/- 0.08 %ID/g for (99m)Tc-TP3982 and (99m)Tc-TP3654, respectively. Twenty-four hours after injection, the corresponding numbers were 17 +/- 0.7 %ID/g, 0.77 +/- 0.1 %ID/g, and 0.23 +/- 0.1 %ID/g. The severalfold greater uptake (21.2-74) of (64)Cu-TP3982 is attributable to the in vivo stability of the agent. CONCLUSION: The results suggest that the uncompromised biologic activity and the significantly greater tumor uptake of (64)Cu-TP3982, combined with the high sensitivity and enhanced resolution of PET imaging, make (64)Cu-TP3982 highly desirable for further studies in PET imaging of oncogene receptors overexpressed in breast and other types of cancers. 相似文献
2.
Nabil M. Abdel-Hamid Tarek K. Mahmoud Shimaa A. Abass Mamdouh M. El-Shishtawy 《Pathophysiology》2018,25(4):433-438
Hepatocellular carcinoma (HCC), represents more than 85% of liver cancers. The diagnosis of HCC may be delayed due to the absence of early, sensitive and specific biomarkers. This study was conducted to investigate whether the expression of thioredoxin (Trx) and glutaredoxin (Grx) is helpful for HCC diagnosis in an experimental model. Twenty male albino rats were equally divided into two groups (HCC and control). Hepatocarcinogenesis was performed by single intraperitoneal (i.p) injection of 200?mg/kg of diethylnitrosamine (DENA). Two weeks later, 0.05% of phenobarbital (PB) was supplied in the drinking water for other 14 weeks. HCC was diagnosed by measuring serum alpha-fetoprotein (AFP) level and histopathological examination. Our results found that hepatic indices alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin were elevated but decreased total protein level. Lipid peroxidation was elevated through increasing hepatic content of MDA with decreased antioxidant parameters like hepatic SOD, CAT activities and GSH. The current study also found that Trx and Grx tissue genes were overexpressed in HCC group significantly, compared to control group. This study substantiated that increased expression of these enzymes may be predictive of outcomes in HCC. 相似文献
3.
Richard O. Phillips Fred S. Sarfo Mohammed K. Abass Justice Abotsi Tuah Wilson Mark Forson Yaw A. Amoako William Thompson Kingsley Asiedu Mark Wansbrough-Jones 《Antimicrobial agents and chemotherapy》2014,58(2):1161-1166
Buruli ulcer, an ulcerating skin disease caused by Mycobacterium ulcerans infection, is common in tropical areas of western Africa. We determined the clinical and microbiological responses to administration of rifampin and streptomycin for 2 weeks followed by administration of rifampin and clarithromycin for 6 weeks in 43 patients with small laboratory-confirmed Buruli lesions and monitored for recurrence-free healing. Bacterial load in tissue samples before and after treatment for 6 and 12 weeks was monitored by semiquantitative culture. The success rate was 93%, and there was no recurrence after a 12-month follow-up. Eight percent had a positive culture 4 weeks after antibiotic treatment, but their lesions went on to heal. The findings indicate that rifampin and clarithromycin can replace rifampin and streptomycin for the continuation phase after rifampin and streptomycin administration for 2 weeks without any apparent loss of efficacy. 相似文献
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Treatment of N,N-dimethylacetamide (DMAC) wastewater is an important step in achieving the sustainable industrial application of DMAC as an organic solvent. This is the first time that treatment of a high concentration of DMAC in real wastewater has been assessed using membrane bioreactor technology. In this study, an anoxic–oxic membrane bioreactor (MBR) was operated over a month to mineralize concentrated DMAC wastewater. Severe membrane fouling occurred during the short-term operation of the MBR as the membrane flux decreased from 11.52 to 5.28 L (m2 h)−1. The membrane fouling was aggravated by the increased amount of protein fractions present in the MBR mixed liquor. Moreover, results from the excitation–emission matrix analysis identified tryptophan and other protein-like related substances as the major membrane-fouling components. Furthermore, analysis of the DMAC degradation mechanism via high performance liquid chromatography (HPLC) and ion chromatography (IC) revealed that the major degradation products were ammonium and dimethylamine (DMA). Although the MBR system achieved the steady removal of DMAC and chemical oxygen demand (COD) by up to 98% and 80%, respectively at DMAC0 ≤ 7548 mg L−1, DMA was found to have accumulated in the treated effluent. Our investigation provides insight into the prospect and challenges of using MBR systems for DMAC wastewater degradation.Treatment of N,N-dimethylacetamide (DMAC) wastewater is an important step in achieving the sustainable industrial application of DMAC as an organic solvent. 相似文献
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Clinical value of 18F-FDG-PET/CT in suspected serious disease with special emphasis on occult cancer
Caspersen Kamilla Bredlund Giannoutsou Nikoletta Gerke Oke Alavi Abass Høilund-Carlsen Poul Flemming Hess Søren 《Annals of nuclear medicine》2019,33(3):184-192
Annals of Nuclear Medicine - Suspected serious disease (SSD) is a disease designation often given to patients with one or more non-specific symptoms of severe disease that could be due to cancer;... 相似文献
9.
Ummarah Kanwal Muhammad Ovais Nasir Abass Khalid Hussain 《Journal of drug targeting》2018,26(4):296-310
Doxorubicin (DOX) is the most effective chemotherapeutic drug developed against broad range of cancers such as solid tumours, transplantable leukemias and lymphomas. Conventional DOX-induced cardiotoxicity has limited its use. FDA approved drugs i.e. non-pegylated liposomal (Myocet®) and pegylated liposomal (Doxil®) formulations have no doubt shown comparatively reduced cardiotoxicity, but has raised new toxicity issues. The entrapment of DOX in biocompatible, biodegradable and safe nano delivery systems can prevent its degradation in circulation minimising its toxicity with increased half-life, enhanced pharmacokinetic profile leading to improved patient compliance. In addition, nano delivery systems can actively and passively target the tumour resulting increase in therapeutic index and decreased side effects of drug. Foreseeing the need of a comprehensive review on DOX nanoformulations, in this article we for the first time have given an updated insight on DOX nano delivery systems. 相似文献
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