全文获取类型
收费全文 | 260篇 |
免费 | 18篇 |
国内免费 | 1篇 |
专业分类
耳鼻咽喉 | 3篇 |
儿科学 | 5篇 |
妇产科学 | 3篇 |
基础医学 | 32篇 |
口腔科学 | 19篇 |
临床医学 | 33篇 |
内科学 | 23篇 |
神经病学 | 4篇 |
特种医学 | 4篇 |
外科学 | 85篇 |
综合类 | 3篇 |
预防医学 | 5篇 |
眼科学 | 6篇 |
药学 | 28篇 |
中国医学 | 5篇 |
肿瘤学 | 21篇 |
出版年
2023年 | 3篇 |
2022年 | 1篇 |
2021年 | 9篇 |
2020年 | 11篇 |
2019年 | 14篇 |
2018年 | 18篇 |
2017年 | 9篇 |
2016年 | 8篇 |
2015年 | 13篇 |
2014年 | 16篇 |
2013年 | 10篇 |
2012年 | 19篇 |
2011年 | 19篇 |
2010年 | 4篇 |
2009年 | 8篇 |
2008年 | 33篇 |
2007年 | 26篇 |
2006年 | 24篇 |
2005年 | 13篇 |
2004年 | 11篇 |
2003年 | 7篇 |
2002年 | 2篇 |
2000年 | 1篇 |
排序方式: 共有279条查询结果,搜索用时 15 毫秒
61.
Prasanth Ganesan Trivadi S. Ganesan Harshvardhan Atreya Krishnarathinam Kannan Venkatraman Radhakrishnan Manikandan Dhanushkodi Thanda Lucy Ann Joshua Shirley Sundersingh Tenali Gnana Sagar 《Indian journal of hematology & blood transfusion》2018,34(3):454-459
Recent reports have shown that excellent survival outcomes can be achieved in adult Burkitt’s lymphoma with the use of DA-EPOCH-R regimen. When compared to earlier intense pediatric-type protocols, this regimen is less toxic. There are limited reports available on the use of this regimen outside the context of clinical trials. We analyzed the outcomes of patients who were treated with the DA-EPOCH-R regimen [Burkitt’s lymphoma (BL), primary mediastinal B cell lymphoma (PMBCL) and HIV-positive patients with diffuse large B cell lymphoma (DLBCL)] at our center over a 3 year period. Baseline characters, responses, and toxicity data was captured from records. Event-free survival (EFS—from therapy initiation till occurrence of event (non-achievement of complete response or relapse) and overall survival (OS—from therapy initiation till death due to any cause) were estimated using Kaplan–Meier method. Among 41 patients [median age 40 years (18–76)], the following diagnoses were included-HIV negative patients (N = 29): BL (N = 24), PMBCL (N = 5); HIV positive patients (N = 12): BL (N = 8), and DLBCL (N = 4). Among those with BL, majority had stage III/IV disease (N = 21/32, 65%). At the completion of planned therapy, 33 had achieved CR (81%). One patient died due to toxicity. The actuarial EFS and OS at 2 years were 80 and 77% respectively for all patients. The OS at 2 years was 100% for PMBCL, 80% for BL and 50% for HIV-positive DLBCL. Majority of the failures in BL were in patients with advanced disease. DA-EPOCH-R can be used in real-world setting and allows treatment of older patients with BL. 相似文献
62.
Paul T. R. Thiruchelvam Chun-Fui Lai Hui Hua Ross S. Thomas Antoni Hurtado William Hudson Andrew R. Bayly Fiona J. Kyle Manikandan Periyasamy Andrew Photiou Alan C. Spivey Eric A. Ortlund Richard J. Whitby Jason S. Carroll R. Charles Coombes Laki Buluwela Simak Ali 《Breast cancer research and treatment》2011,127(2):385-396
Estrogen receptor-?? (ER) is expressed in the great majority of breast cancers, and the inhibition of ER action is a key part of breast cancer treatment. The inhibition of ER action is achieved using anti-estrogens, primarily tamoxifen, and with aromatase inhibitors that inhibit estrogen biosynthesis, thereby preventing ER activation. However, resistance to these therapies is common. With the aim of identifying new molecular targets for breast cancer therapy, we have identified the liver receptor homolog-1 (LRH-1) as an estrogen-regulated gene. RNA interference and over-expression studies were used to investigate the role of the LRH-1 in regulating breast cancer growth and to identify the targets of an LRH-1 action. Promoter recruitment was determined using reporter gene and chromatin immunoprecipitation (ChIP) assays. We show that LRH-1 regulates breast cancer cell growth by regulating the ER expression. Reporter gene and in vitro DNA-binding assays identified an LRH-1-binding site in the ER gene promoter, and ChIP assays have demonstrated in vivo binding at this site. We also provide evidence for new LRH-1 variants in breast cancer cells arising from the use of alternative promoters. Previous studies have shown that LRH-1 functions in estrogen biosynthesis by regulating aromatase expression. Our findings extend this by highlighting LRH-1 as a key regulator of the estrogen response in breast cancer cells through the regulation of ER expression. Hence, inhibition of LRH-1 could provide a powerful new approach for the treatment of endocrine-resistant breast cancer. 相似文献
63.
Robert S. Tolhurst Ross S. Thomas Fiona J. Kyle Hetal Patel Manikandan Periyasamy Andrew Photiou Paul T. R. Thiruchelvam Chun-Fui Lai Marwa Al-sabbagh Rosemary A. Fisher Sayka Barry Tatjana Crnogorac-Jurcevic Lesley-Ann Martin Mitch Dowsett R. Charles Coombes Tahereh Kamalati Simak Ali Laki Buluwela 《Breast cancer research and treatment》2011,128(2):357-368
Estrogen receptor-?? (ER??) positive breast cancer frequently responds to inhibitors of ER?? activity, such as tamoxifen, and/or to aromatase inhibitors that block estrogen biosynthesis. However, many patients become resistant to these agents through mechanisms that remain unclear. Previous studies have shown that expression of ER?? in ER??-negative breast cancer cell lines frequently inhibits their growth. In order to determine the consequence of ER?? over-expression in ER??-positive breast cancer cells, we over-expressed ER?? in the MCF-7 breast cancer cell line using adenovirus gene transduction. ER?? over-expression led to ligand-independent expression of the estrogen-regulated genes pS2 and PR and growth in the absence of estrogen. Interestingly, prolonged culturing of these cells in estrogen-free conditions led to the outgrowth of cells capable of growth in cultures from ER?? transduced, but not in control cultures. From these cultures a line, MLET5, was established which remained ER??-positive, but grew in an estrogen-independent manner. Moreover, MLET5 cells were inhibited by anti-estrogens showing that ER?? remains important for their growth. Gene expression microarray analysis comparing MCF-7 cells with MLET5 highlighted apoptosis as a major functional grouping that is altered in MLET5 cells, such that cell survival would be favoured. This conclusion was further substantiated by the demonstration that MLET5 show resistance to etoposide-induced apoptosis. As the gene expression microarray analysis also shows that the apoptosis gene set differentially expressed in MLET5 is enriched for estrogen-regulated genes, our findings suggest that transient over-expression of ER?? could lead to increased cell survival and the development of estrogen-independent growth, thereby contributing to resistance to endocrine therapies in breast cancer patients. 相似文献
64.
Kaliaperumal Krishnaraj Mulla Joghi Nanjan Chandrasekar Mulla Joghi Nanjan Selvadurai Muralidharan Duraikannu Manikandan 《Saudi Pharmaceutical Journal》2012,20(3):239-248
A natural polysaccharide was isolated from the seeds of Delonix regia. The isolated polysaccharide could maintain aqueous equilibrium between the dosage form and the surrounding medium due to its massive competence of water absorption (80.72%) and swelling index (266.7%). The Scanning Electron Micrograph of a polysaccharide exhibits rough surface with pores and crevices, hence, the drug release will be retarded because of the drug particles entrapment in the pores and crevices. Further, the surface tension of polysaccharide is higher than that of water, which may facilitate sustained release of drugs from dosage forms. An antipsychotic drug, quetiapine fumarate has a short half-life of 6 h and administered multiple times per day. Hence the quetiapine fumarate oral sustained release tablets were formulated using this polysaccharide in the concentration of 5–30% to avoid the side effects and increase patient compliance. Dissolution of the developed tablets with 25% polysaccharide content showed a better release profile than the other batches (5–20%) at the end of 12 h. The strong matrix complex has low solubility in water, it does not dissolve rapidly and the drug continues to diffuse through the gel layer at a consistent rate. Drug release from the matrix tablets follows matrix type except F-4 and F-5 which follow first order and Hix.crow type. The bioavailability study was carried out using healthy male New Zealand white rabbits that show the AUC(0–inf) value for developed SR tablets is 1.44 times higher than the reference thus, indicating more efficient and sustained drug delivery capable of maintaining plasma drug levels better. 相似文献
65.
66.
Ramamurthi Vidya Priyadarsini Govindarajah Vinothini Ramalingam Senthil Murugan Palrasu Manikandan Siddavaram Nagini 《Nutrition and cancer》2013,65(2):218-226
Epidemiological studies have consistently demonstrated the protective effects of dietary phytochemicals against cancer risk. Quercetin, a ubiquitous dietary flavonoid, has attracted considerable attention owing to its potent antioxidant and antiproliferative activities. The present study was designed to investigate the chemopreventive as well as the therapeutic ability of quercetin to modulate the key hallmark capabilities of 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinomas. We analyzed the expression of markers associated with cell proliferation and survival (PCNA, p21, p53, cyclin D1, GST-P), apoptosis (Fas, Fas-L, Bcl-2 family proteins, cytochrome-C, Apaf-1, caspases, PARP, survivin, cFLIP, API1), invasion (MMPs, TIMP-2, RECK), angiogenesis (PlGF, VEGF, VEGF receptors, HIF-1α), as well as the epigenetic markers (HDAC-1, DNMT1) by immunohistochemical, Western blot, and RT-PCR analyses. Simultaneous administration of quercetin to DMBA-painted hamsters reduced tumor incidence and tumor burden, while posttreatment of quercetin resulted in a significant tumor growth delay. In addition, quercetin administration induced cell cycle arrest and apoptosis and blocked invasion and angiogenesis. We found a positive correlation between the inhibition of HDAC-1 and DNMT1 by quercetin and its anticancer properties. A dietary phytochemical such as quercetin that modulates a plethora of molecules offers promise as an ideal candidate for multitargeted cancer prevention and therapy. 相似文献
67.
Kannan S Karthiga B Sivapatha Sundharam R Manikandan 《Indian journal of dental research》2006,17(1):50-53
Binkley and Johnson first reported this syndrome in 1951. But it was in 1960, Gorlin-Goltz established the association of basal cell epithelioma, jaw cyst and bifid ribs, a combination which is now frequently known as Gorlin-Goltz syndrome as well as Nevoid Basal Cell Carcinoma Syndrome (NBCCS). NBCCS is inherited as an autosomal dominant trait with high penetrance and variable expressivity. NBCCS is characterized by variety of cutaneous, dental, osseous, opthalmic, neurologic and sexual abnormalities. One such case of Gorlin-Goltz syndrome is reported here with good illustrations. 相似文献
68.
The authors report on a 6-year-old boy who presented with a tense subgaleal hematoma and proptosis 2 weeks after a minor head injury that were successfully managed by continuous closed-system drainage and blood transfusion. At evaluation he was found to have a transient mild factor XIII deficiency. 相似文献
69.
70.
Nikita Mehra Prasanth Ganesan Trivadi S. Ganesan Surendran Veeriah Abirami Boopathy Venkatraman Radhakrishnan Manikandan Dhanushkodi Swaminathan Rajaraman Sevaluxmy Ganesharajah Tenali Gnana Sagar 《Medical oncology (Northwood, London, England)》2018,35(1):12
Chemotherapy-induced nausea–vomiting (CINV) compromises the quality of life of patients with cancer. We present data on the effectiveness of olanzapine after failure of aprepitant in patients receiving highly emetogenic chemotherapy (HEC). A single-center prospective study was conducted, where patients ≥ 18 years who failed aprepitant, palonosetron, dexamethasone (APD) received olanzapine, palonosetron and dexamethasone (OPD) in the subsequent cycle of HEC. Failure of APD was defined as occurrence of ≥ grade 2 acute and/or delayed nausea ± vomiting. Response rates were compared with what was achieved in their previous cycle with the use of APD in the acute (0–24 h), delayed (24–120 h) and overall (0–120 h) periods after the start of HEC. Impact on life was assessed using the MD Anderson Symptom Inventory (MDASI). Fifty-five patients failed APD and received OPD in the subsequent cycle; 54 were evaluable for response. Complete response rate for OPD versus APD is 80 versus 20% (acute period), 90 versus 18% (delayed period) and 74 versus 5% (overall period), and no nausea rate for OPD versus APD is 57 versus 13% (acute), 59 versus 15% (delayed) and 48 versus 0% (overall period), p < 0.001 for all comparisons. MDASI scores showed significant improvement after switching to OPD. A mild increase in drowsiness noted in patients receiving OPD did not affect daily life in most patients. In patients receiving HEC and failing CINV prophylaxis with APD, switching to OPD regimen in the subsequent cycle greatly improves control of vomiting, increases “no nausea” rates and significantly reduces symptom severity scores. 相似文献