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61.
62.
J.G. Hiremath A. Rajeshkumar D. Ickowicz A.J. Domb 《Journal of drug delivery science and technology.》2013,23(5):439-444
Paclitaxel-loaded nanosized particles (NPs) of poly(lactic acid co castor oil) 60:40 % w/w- (p(DLLA:CO) were prepared by nanoprecipitation method and lyophilized using cryoprotectants. The prepared nanoparticles were evaluated for encapsulation efficiency and drug release. The formulations were also characterized by Fourier transform infrared (FTIR), powder X-ray diffraction (PXRD), scanning electron microscope (SEM) and particle size. From the SEM microphotographs, NPs were obtained in the form of long, flat scales which are similar to rod/bone and rose flower-like shaped nanosized drug delivery systems. FTIR, XRD and DSC results proved that the drug is encapsulated in the polymeric matrix in the amorphous state. Formulations obtained were below 400 nm. 相似文献
63.
Georg Feldmann Anjali Mishra Savita Bisht Collins Karikari Ignacio Garrido-Laguna Zeshaan Rasheed Niki A Ottenhof Tikva Dadon Hector Alvarez Volker Fendrich NV Rajeshkumar William Matsui Peter Brossart Manuel Hidalgo Rajat Bannerji Anirban Maitra Barry D Nelkin 《Cancer biology & therapy》2011,12(7):598-609
Pancreatic cancer is one of the most lethal of human malignancies, and potent therapeutic options are lacking. Inhibition of cell cycle progression through pharmacological blockade of cyclin-dependent kinases (CDK) has been suggested as a potential treatment option for human cancers with deregulated cell cycle control. Dinaciclib (SCH727965) is a novel small molecule multi-CDK inhibitor with low nanomolar potency against CDK1, CDK2, CDK5 and CDK9 that has shown favorable toxicity and efficacy in preliminary mouse experiments, and has been well tolerated in Phase I clinical trials. In the current study, the therapeutic efficacy of SCH727965 on human pancreatic cancer cells was tested using in vitro and in vivo model systems. Treatment with SCH727965 significantly reduced in vitro cell growth, motility and colony formation in soft agar of MIAPaCa-2 and Pa20C cells. These phenotypic changes were accompanied by marked reduction of phosphorylation of Retinoblastoma (Rb) and reduced activation of RalA. Single agent therapy with SCH727965 (40 mg/kg i.p. twice weekly) for 4 weeks significantly reduced subcutaneous tumor growth in 10/10 (100%) of tested low-passage human pancreatic cancer xenografts. Treatment of low passage pancreatic cancer xenografts with a combination of SCH727965 and gemcitabine was significantly more effective than either agent alone. Gene Set Enrichment Analysis identified overrepresentation of the Notch and Transforming Growth Factor-β (TGFβ) signaling pathways in the xenografts least responsive to SCH727965 treatment. Treatment with the cyclin-dependent kinase inhibitor SCH727965 alone or in combination is a highly promising novel experimental therapeutic strategy against pancreatic cancer.Key words: pancreatic cancer, xenograft mouse models, cyclin-dependent kinases, SCH727965, dinaciclib, cell cycle, translational research 相似文献
64.
I Garrido-Laguna A C Tan M Uson M Angenendt W W Ma M C Villaroel M Zhao N V Rajeshkumar A Jimeno R Donehower C Iacobuzio-Donahue M Barrett M A Rudek B Rubio-Viqueira D Laheru M Hidalgo 《British journal of cancer》2010,103(5):649-655
Background:
The purpose of this work was to determine the efficacy of inhibiting mammalian target of rapamycin (mTOR) in pancreatic cancer preclinical models and translate preclinical observations to the clinic.Methods:
Temsirolimus (20 mg Kg−1 daily) was administered to freshly generated pancreatic cancer xenografts. Tumour growth inhibition was determined after 28 days. Xenografts were characterised at baseline by gene expression and comparative genomic hybridisation. Patients with advanced, gemcitabine-resistant pancreatic cancer were treated with sirolimus (5 mg daily). The primary end point was 6-month survival rate (6mSR). Correlative studies included immunohistochemistry assessment of pathway expression in baseline tumours, drug pharmacokinetics (PKs), response assessment by FDG-PET and pharmacodynamic effects in peripheral-blood mononuclear cells (PBMCs).Results:
In all, 4 of 17 xenografts (23%) responded to treatment. Sensitive tumours were characterised by gene copy number variations and overexpression of genes leading to activation of the PI3K/Akt/mTOR pathway. Activation of p70S6K correlated with drug activity in the preclinical studies. Sirolimus was well tolerated in the clinic, showed predictable PKs, exerted pathway inhibition in post-treatment PBMCs and resulted in a 6mSR of 26%. No correlation, however, was found between activated p70S6K in tumour tissues and anti-tumour effects.Conclusion:
Sirolimus activity in pancreatic cancer was marginal and not predicted by the selected biomarker. 相似文献65.
66.
Atrial septostomy with a predefined diameter using a novel occlutech atrial flow regulator improves symptoms and cardiac index in patients with severe pulmonary arterial hypertension 下载免费PDF全文
67.
高位胸段硬膜外麻醉下清醒病人的冠状动脉搭桥手术 总被引:2,自引:0,他引:2
目的 了解在高位胸段硬膜外麻醉下避免全麻行非体外循环心脏跳动下冠状动脉搭桥手术的可行性。方法 硬膜外麻醉下对 2 5例清醒病人行非体外循环心脏跳动下冠状动脉搭桥手术 ,没有气管插管全麻 ,所有病人在手术前晚行硬膜外置管。结果 总共搭桥 71支 (1支 11例 ,2支 5例 ,3支 6例 ,4支 3例 )。除 1例因为术中出现室颤转为全麻和体外循环外 ,2 4例在硬外麻作为唯一麻醉下完成非体外循环心脏跳动下冠状动脉搭桥手术。除 2例行左胸小切口外其余行正中切口 ;其中 6例为再次手术 ;平均每例搭桥2 8支 ,没有手术死亡。术后在复苏室和病房住院时间分别为 (16 2± 4 2 )h和 (3 2 4± 1 2 )d。结论 本组的早期经验提示在没有气管插管全麻、病人清醒下可以行多支冠状动脉搭桥术 相似文献
68.
Gaddipati JP Rajeshkumar NV Thangapazham RL Sharma A Warren J Mog SR Singh AK Maheshwari RK 《Journal of experimental therapeutics & oncology》2004,4(3):203-212
Rasayanas are a group of herbal formulations and are used to improve health of the body. Recent studies have demonstrated the immunostimulatory and antioxidant activities of some of these rasayanas and their usefulness in tumor regression. The objective of the study is to evaluate Brahma rasayana for the inhibition of tumor development and prevention of metastasis in vivo using Copenhagen rats and MAT-LyLu cell model system. Copenhagen rats injected with MAT-LyLu cells were treated with Brahma rasayana once daily. This treatment was followed from the second day of cell inoculation until the end of the experiment. The study comprises a comparison of survival time, body weight, tumor incidence, tumor size, tumor weight, histopathological examination of the lung metastasis and serum testosterone levels between rasayana treated and control animals. Brahma rasayana treatment resulted in a 25-37% decrease in palpable tumor incidence, a delay of 1-2 weeks in the tumor occurrence, lower mean tumor volumes, by as much as 14-35% and significant reduction in tumor weight and lung metastasis in comparison to untreated controls. The Ayurvedic poly herbal preparation, Brahma rasayana may play a beneficial role in preventing tumor incidence, tumor growth and metastatic spread. These are inexpensive preparations that have little or no adverse side effects with a potential as lead chemopreventive compounds and which might prove useful for the treatment of disorders such as human prostate cancer. 相似文献
69.
DB Bethell TT Hien LT Phi NP Day H Vinh NM Duong NV Len LV Chuong NJ White 《Archives of disease in childhood》1996,74(1):44-46
The aim of the study was to document the effects of short courses of fluoroquinolones given during an outbreak of multidrug resistant typhoid fever in southern Viet Nam on the growth of children over a period of two years. In a prospective cohort study, 326 Vietnamese children aged between 1 and 14 years were followed up for two years after receiving either ciprofloxacin (70 mg/kg given over 7 d) (n = 173) or ofloxacin (45-50 mg/kg given over 3-5 d) (n = 153) for suspected typhoid fever. Growth velocity and weight for height were compared with an age matched control group of children from the same locality (n = 223) who had not contracted typhoid or received any fluoroquinolones. In the ofloxacin and ciprofloxacin treated patients there was no evidence of acute joint toxicity, nor of any joint symptoms attributable to either of the fluoroquinolones. There was no difference in expected weight for height measurements between the three groups of children over the two year period. During the first year, height velocity in ciprofloxacin treated children was greater than in either ofloxacin treated children or untreated controls. Height velocity in the latter two groups was not significantly different. After two years height velocity was similar in the three groups. The results support the use of short course fluoroquinolone treatment in childhood typhoid, especially when caused by strains resistant to other antibiotics. 相似文献
70.
Effect of Picrorrhiza kurroa extract on transplanted tumours and chemical carcinogenesis in mice 总被引:2,自引:0,他引:2
Anti-tumour and anti-carcinogenic activity of Picrorrhiza kurroa extract were studied in mice. Administration of 20-methylcholanthrene (20 MC) produced 100% induction of sarcoma in control mice, whereas the tumour incidence and tumour related deaths were significantly inhibited by the oral administration of P. kurroa extract 150 and 750 mg/kg body weight, respectively. The extract was also found to reduce the volume of transplanted solid tumours induced by Dalton's lymphoma ascites (DLA) tumour cell lines and increased the life span of ascites tumour bearing mice. P. kurroa extract inhibited yeast topoisomerase I and II enzyme activity when tested on Saccharomyces cerevisiae mutant cell cultures. The extract did not inhibit the enzyme involved in the activation of carcinogen and the cell cycle regulatory enzyme cdc2 kinase. 相似文献