全文获取类型
收费全文 | 113篇 |
免费 | 12篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 1篇 |
妇产科学 | 2篇 |
基础医学 | 12篇 |
口腔科学 | 1篇 |
临床医学 | 7篇 |
内科学 | 23篇 |
外科学 | 9篇 |
综合类 | 2篇 |
预防医学 | 9篇 |
眼科学 | 1篇 |
药学 | 7篇 |
肿瘤学 | 50篇 |
出版年
2023年 | 1篇 |
2022年 | 8篇 |
2021年 | 7篇 |
2020年 | 10篇 |
2019年 | 8篇 |
2018年 | 4篇 |
2017年 | 3篇 |
2016年 | 3篇 |
2015年 | 6篇 |
2014年 | 6篇 |
2013年 | 5篇 |
2012年 | 11篇 |
2011年 | 9篇 |
2010年 | 7篇 |
2009年 | 3篇 |
2008年 | 11篇 |
2007年 | 8篇 |
2006年 | 5篇 |
2005年 | 1篇 |
2004年 | 2篇 |
2003年 | 4篇 |
2002年 | 2篇 |
1989年 | 1篇 |
排序方式: 共有125条查询结果,搜索用时 15 毫秒
1.
Sebastian Mondaca Walid K. Chatila David Bates Jaclyn F. Hechtman Andrea Cercek Neil H. Segal Zsofia K. Stadler Anna M. Varghese Ritika Kundra Marinela Capanu Jinru Shia Nikolaus Schultz Leonard Saltz Rona Yaeger 《Clinical colorectal cancer》2019,18(1):e39-e52
Background
Treatment of advanced anal squamous cell cancer (SCC) is usually with the combination of cisplatin and 5-fluorouracil, which is associated with heterogeneous responses across patients and significant toxicity. We examined the safety and efficacy of a modified schedule, FOLFCIS (leucovorin, fluorouracil, and cisplatin), and performed an integrated clinical and genomic analysis of anal SCC.Patients and Methods
We reviewed all patients with advanced anal SCC receiving first-line FOLFCIS chemotherapy – essentially a FOLFOX (leucovorin, fluorouracil, and oxaliplatin) schedule with cisplatin substituted for oxaliplatin – in our institution between 2007 and 2017, and performed deep sequencing to identify genomic markers of response and key genomic drivers.Results
Fifty-three patients with advanced anal SCC (48 metastatic; 5 unresectable, locally advanced) received first-line FOLFCIS during this period; all were platinum-naive. The response rate was 48% (95% confidence interval [CI], 32.6%-63%). With a median follow-up of 41.6 months, progression-free survival and overall survival were 7.1 months (95% CI, 4.4-8.6 months) and 22.1 months (95% CI, 16.9-28.1 months), respectively. Among all patients with advanced anal SCC that underwent sequencing during the study period, the most frequent genomic alterations consisted of chromosome 3q amplification (51%) and mutations in PIK3CA (29%) and KMT2D (22%). No genomic alteration correlated with response to platinum-containing treatment. Although there were few cases, patients with human papillomavirus-negative anal SCC did not appear to benefit from FOLFCIS, and all harbored distinct genomic profiles with TP53, TERT promoter, and CDKN2A mutations.Conclusions
FOLFCIS appears effective and safe as first-line chemotherapy in patients with advanced anal SCC and represents an alternative treatment option for these patients. 相似文献2.
The detection of rare deleterious variants is the preeminent current technical challenge in statistical genetics. Sorting the deleterious from neutral variants at a disease locus is challenging because of the sparseness of the evidence for each individual variant. Hierarchical modeling and Bayesian model uncertainty are two techniques that have been shown to be promising in pinpointing individual rare variants that may be driving the association. Interpreting the results from these techniques from the perspective of multiple testing is a challenge and the goal of this article is to better understand their false discovery properties. Using simulations, we conclude that accurate false discovery control cannot be achieved in this framework unless the magnitude of the variants' risk is large and the hierarchical characteristics have high accuracy in distinguishing deleterious from neutral variants. 相似文献
3.
Caitlin A. McIntyre MD Sharon A. Lawrence MD Allison L. Richards PhD Joanne F. Chou MPH Winston Wong MD Marinela Capanu PhD Michael F. Berger PhD Mark T. A. Donoghue PhD Kenneth H. Yu MD Anna M. Varghese MD David P. Kelsen MD Wungki Park MD Vinod P. Balachandran MD T. Peter Kingham MD Michael I. D’Angelica MD Jeffrey A. Drebin MD PhD William R. Jarnagin MD Christine A. Iacobuzio-Donahue MD PhD Peter J. Allen MD Eileen M. O’Reilly MD 《Cancer》2020,126(17):3939-3949
4.
5.
Sebastian P. Mondaca MD Dazhi Liu PharmD BCOP Jessica R. Flynn Sandy Badson Stefan Hamaway BS Mrinal M. Gounder MD Danny N. Khalil MD PhD Alexander E. Drilon MD Bob T. Li MD MPH Komal L. Jhaveri MD Alison M. Schram MD Katherine E. Kargus RN Mary Kate Kasler DNP MSN Natalie M. Blauvelt Neil H. Segal MD PhD Marinela Capanu PhD Margaret K. Callahan MD PhD David M. Hyman MD Maya Gambarin-Gelwan MD James J. Harding MD 《Cancer》2020,126(22):4967-4974
6.
7.
Åke Borg Robert W. Haile Kathleen E. Malone Marinela Capanu Ahn Diep Therese Törngren Sharon Teraoka Colin B. Begg Duncan C. Thomas Patrick Concannon Lene Mellemkjaer Leslie Bernstein Lina Tellhed Shanyan Xue Eric R. Olson Xiaolin Liang Jessica Dolle Anne‐Lise Børresen‐Dale Jonine L. Bernstein 《Human mutation》2010,31(3):E1200-E1240
BRCA1 and BRCA2 screening in women at high‐risk of breast cancer results in the identification of both unambiguously defined deleterious mutations and sequence variants of unknown clinical significance (VUS). We examined a population‐based sample of young women with contralateral breast cancer (CBC, n=705) or unilateral breast cancer (UBC, n=1398). We identified 470 unique sequence variants, of which 113 were deleterious mutations. The remaining 357 VUS comprised 185 unique missense changes, 60% were observed only once, while 3% occurred with a frequency of >10%. Deleterious mutations occurred three times more often in women with CBC (15.3%) than in women with UBC (5.2%), whereas combined, VUS were observed in similar frequencies in women with CBC and UBC. A protein alignment algorithm defined 16 rare VUS, occurring at highly conserved residues and/or conferring a considerable biochemical difference, the majority located in the BRCA2 DNA‐binding domain. We confirm a multiplicity of BRCA1 and BRCA2 VUS that occur at a wide range of allele frequencies. Although some VUS inflict chemical differences at conserved residues, suggesting a deleterious effect, the majority are not associated with an increased risk of CBC. © 2010 Wiley‐Liss, Inc. 相似文献
8.
Larisa Daniela Sandulescu Cristiana Marinela Urhut Sarmis Marian Sandulescu Ana-Maria Ciurea Sergiu Marian Cazacu Sevastita Iordache 《World journal of hepatology》2021,13(12):1892-1908
Hepatic hemangioma is usually detected on a routine ultrasound examination because of silent clinical behaviour. The typical ultrasound appearance of hemangioma is easily recognizable and quickly guides the diagnosis without the need for further investigation. But there is also an entire spectrum of atypical and uncommon ultrasound features and our review comes to detail these particular aspects. An atypical aspect in standard ultrasound leads to the continuation of explorations with an imaging investigation with contrast substance [ultrasound/ computed tomography/or magnetic resonance imaging (MRI)]. For a clinician who practices ultrasound and has an ultrasound system in the room, the easiest, fastest, non-invasive and cost-effective method is contrast enhanced ultrasound (CEUS). Approximately 85% of patients are correctly diagnosed with this method and the patient has the correct diagnosis in about 30 min without fear of malignancy and without waiting for a computer tomography (CT)/MRI appointment. In less than 15% of patients CEUS does not provide a conclusive appearance; thus, CT scan or MRI becomes mandatory and liver biopsy is rarely required. The aim of this updated review is to synthesize the typical and atypical ultrasound aspects of hepatic hemangioma in the adult patient and to propose a fast, non-invasive and cost-effective clinical-ultrasound algorithm for the diagnosis of hepatic hemangioma. 相似文献
9.
Larisa Maria Badau Andrei Dorin Ciocoiu Cristina Marinela Oprean Nusa Alina Segarceanu Adelina Gheju Brigitha Vlaicu 《Current oncology (Toronto, Ont.)》2022,29(3):1890
The safety profile and effectiveness of existing anti-HER2-targeted therapies have not been evaluated in patients with breast cancer and visceral crisis. We report the case of a 26-year-old woman who was diagnosed with advanced HER2-positive breast cancer and initially treated with curative intent therapy in a neoadjuvant setting, using Trastuzumab and Pertuzumab in combination with Docetaxel; her cancer recurred two years later, with liver metastases and pulmonary lymphangitic carcinomatosis, causing visceral crisis. Furthermore, the patient’s clinical status worsened when she developed respiratory failure, hepatomegaly and a severe hepatocytolysis. Since the patient was free of disease more than six months, we started with Paclitaxel half dose because of the hepatic dysfunction, and we gradually reintroduced Trastuzumab and then Pertuzumab. In the meantime, the patient changed her lifestyle by increasing her consumption of fresh fruits and vegetables and fiber and reducing her intake of processed meat, dairy and sugar. As a result, the patient showed a significant improvement in her respiratory symptoms and liver tests in less than two months. Imaging reevaluation showed partial remission of liver metastases and pulmonary lymphangitic carcinomatosis. She underwent seven months of dual anti-HER2 blockade before relapsing cerebrally. Our results suggest that the sequential combination therapy with Trastuzumab, Pertuzumab and Paclitaxel presented in this study, associated with a healthy lifestyle, may be a good management for recurrent HER2-positive breast cancer with pulmonary visceral crisis and severe liver dysfunction. 相似文献
10.
BACKGROUND: Response rates to systemic chemotherapy are low after tumor progression on oxaliplatin regimens. Hepatic arterial infusion (HAI) therapy in patients with tumor progression is a viable alternative. PATIENTS AND METHODS: Thirty-nine heavily pre-treated patients (all receiving prior oxaliplatin) with unresectable colorectal hepatic metastases were treated with systemic CPT-11 and concurrent HAI floxuridine (FUDR) and dexamethasone (DEX). RESULTS: Partial responses were seen in 44% of patients. Median time to hepatic progression was 8.6 months, and median time to overall progression was 6.5 months. Median survival from time of initiation of HAI was 20.1 months [95% confidence interval (CI) 16.9-21.4] and from the initiation of treatment of metastatic disease, 32.01 months (95% CI 29.1-34.6). After a median follow-up of 19.1 months, seven patients (18%) proceeded to potentially curative surgery. Grade 3/4 toxic effects included neutropenia (13%), diarrhea (15%), intra-abdominal hemorrhage (2%), and bleeding duodenal ulcer (2%). Elevated liver function tests were seen, including bilirubin concentration >3 mg/dl (7%), alkaline phosphatase 2X baseline (20%), and aspartate aminotransferase >3X baseline (26%). CONCLUSIONS: HAI FUDR/DEX plus systemic CPT-11 achieves a response rate of 44% and a median overall survival of 20 months in heavily pre-treated patients with colorectal hepatic metastases all receiving previous oxaliplatin; 18% of patients proceeded to surgical resection or ablation. 相似文献