全文获取类型
收费全文 | 574篇 |
免费 | 49篇 |
国内免费 | 2篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 26篇 |
妇产科学 | 4篇 |
基础医学 | 30篇 |
口腔科学 | 25篇 |
临床医学 | 61篇 |
内科学 | 256篇 |
皮肤病学 | 9篇 |
神经病学 | 16篇 |
特种医学 | 17篇 |
外科学 | 48篇 |
综合类 | 5篇 |
预防医学 | 10篇 |
眼科学 | 2篇 |
药学 | 23篇 |
肿瘤学 | 92篇 |
出版年
2023年 | 6篇 |
2022年 | 22篇 |
2021年 | 24篇 |
2020年 | 25篇 |
2019年 | 26篇 |
2018年 | 22篇 |
2017年 | 27篇 |
2016年 | 15篇 |
2015年 | 16篇 |
2014年 | 27篇 |
2013年 | 25篇 |
2012年 | 44篇 |
2011年 | 38篇 |
2010年 | 23篇 |
2009年 | 23篇 |
2008年 | 45篇 |
2007年 | 29篇 |
2006年 | 26篇 |
2005年 | 30篇 |
2004年 | 32篇 |
2003年 | 27篇 |
2002年 | 11篇 |
2001年 | 7篇 |
2000年 | 1篇 |
1999年 | 3篇 |
1998年 | 5篇 |
1997年 | 7篇 |
1996年 | 8篇 |
1995年 | 4篇 |
1993年 | 5篇 |
1992年 | 2篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1986年 | 1篇 |
1984年 | 1篇 |
1983年 | 3篇 |
1982年 | 1篇 |
1980年 | 1篇 |
1978年 | 3篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 2篇 |
排序方式: 共有625条查询结果,搜索用时 24 毫秒
11.
目的构建并鉴定靶向人ERRα基因的小分子干扰RNA的慢病毒载体。方法针对ERRαmRNA设计了4条si RNA,并构建pGCSIL-GFP-siERRα慢病毒质粒,PCR扩增阳性克隆并测序鉴定。用pGCSIL-GFP-siERRα、pHelp-er1.0和pHelper2.0质粒共转染293T细胞包装产生慢病毒,测定病毒滴度。将慢病毒干扰RNA及含有ERRα过表达载体共转染293T细胞,Western-blot检测ERRα表达,观察蛋白表达抑制效果。结果 PCR和测序结果与设计的干扰序列一致,病毒滴度达2×109TU/ml。转染细胞中ERRα蛋白表达显著降低。结论成功构建高表达、高效率的人ERRα基因小分子干扰RNA慢病毒载体,为进一步研究ERRα在细胞核内转导中的作用机制和靶向ERRα治疗奠定基础。 相似文献
12.
13.
Shaji Kumar Lawrence Baizer Natalie S. Callander Sergio A. Giralt Jens Hillengass Boris Freidlin Antje Hoering Paul G. Richardson Elena I. Schwartz Anthony Reiman Suzanne Lentzsch Philip L. McCarthy Sundar Jagannath Andrew J. Yee Richard F. Little Noopur S. Raje 《Blood cancer journal》2022,12(6)
A wide variety of new therapeutic options for Multiple Myeloma (MM) have recently become available, extending progression-free and overall survival for patients in meaningful ways. However, these treatments are not curative, and patients eventually relapse, necessitating decisions on the appropriate choice of treatment(s) for the next phase of the disease. Additionally, an important subset of MM patients will prove to be refractory to the majority of the available treatments, requiring selection of effective therapies from the remaining options. Immunomodulatory agents (IMiDs), proteasome inhibitors, monoclonal antibodies, and alkylating agents are the major classes of MM therapies, with several options in each class. Patients who are refractory to one agent in a class may be responsive to a related compound or to a drug from a different class. However, rules for selection of alternative treatments in these situations are somewhat empirical and later phase clinical trials to inform those choices are ongoing. To address these issues the NCI Multiple Myeloma Steering Committee formed a relapsed/refractory working group to review optimal treatment choices, timing, and sequencing and provide recommendations. Additional issues considered include the role of salvage autologous stem cell transplantation, risk stratification, targeted approaches for genetic subsets of MM, appropriate clinical trial endpoints, and promising investigational agents. This report summarizes the deliberations of the working group and suggests potential avenues of research to improve the precision, timing, and durability of treatments for Myeloma.Subject terms: Combination drug therapy, Cancer therapeutic resistance, Targeted therapies 相似文献
14.
15.
16.
Rahma Warsame Soo Mee Bang Shaji K. Kumar Morie A. Gertz Martha Q. Lacy Francis Buadi David Dingli Suzanne R. Hayman Prashant Kapoor Robert A. Kyle Nelson Leung John A. Lust Stephen J. Russell Thomas E. Witzig Steven R. Zeldenrust S. Vincent Rajkumar Angela Dispenzieri 《European journal of haematology》2014,92(6):485-490
Immunoglobulin light chain (AL) Amyloidosis is a condition whereby misfolded proteins generated by plasma cells deposit in tissues causing organ dysfunction. Chemotherapy and autologous stem cell transplant when eligible are standard treatment options. Several studies report long‐term outcomes of patients post‐transplant. However, there is a paucity of literature describing outcomes of relapsed patients post‐transplant. We performed a retrospective study to assess outcomes and therapies employed upon relapse after transplant. Between 1996 and 2009, 410 patients received transplant at the Mayo Clinic as first‐line therapy. Of those patients, 42 (10%) died within 3 months of transplant, 64 (16%) died without documented relapse, 158 (38%) were alive without documented progression, and 146 (36%) had documented progression. Those 146 patients are the subject of our study, and their median time to hematologic relapse/progression was 23.6 months (95%CI 18.3, 26.3 months). Their median overall survival and 5‐yrs overall survival from post‐transplant relapse/progression was 51.7 months (95%CI 34.1–62.3) and 39%, respectively. The most common first regimen for treatment after relapse was lenalidomide or thalidomide. In conclusion, our study indicates that patients with AL amyloidosis fare well post‐transplant relapse/progression. Additionally, it provides a yardstick to design clinical trials to determine best treatment options. 相似文献
17.
ATP7B mutations in families in a predominantly Southern Indian cohort of Wilson's disease patients. 总被引:4,自引:0,他引:4
S Santhosh R V Shaji C E Eapen V Jayanthi S Malathi M Chandy M Stanley S Selvi G Kurian G M Chandy 《Indian journal of gastroenterology》2006,25(6):277-282
OBJECTIVE: To analyze ATP7B mutations in Wilson's disease (WD) patients from the Indian subcontinent and to correlate these with WD phenotype. METHODS: We studied 27 WD patients from 25 unrelated families. Twenty-two families were from three southern Indian states - Tamil Nadu andhra Pradesh and Kerala. We applied conformation- sensitive gel electrophoresis (CSGE) to screen for the mutations in patients and their families. PCR products exhibiting aberrant patterns in CSGE were subjected to direct DNA sequencing. As siblings affected by WD within a family share identical ATP7B genotype, we compared WD phenotype among affected siblings within families. RESULTS: ATP7B mutations were detected in 22 of the 25 probands -13 were homozygotes and 9 were compound heterozygotes. Eleven novel mutations were detected. Only two common mutations were found: G3182A in 4 (16%) and C813A in 3 (12%) probands. 'Hot spots' for ATP7B mutations were exons 18 and 13. Lack of common dominant mutations prevented correlation of individual ATP7B mutations with WD phenotype. Symptomatic WD in a live sibling was not found in any family. In 8 families, a sibling died of presumed WD - in 6 of these, WD phenotype was identical to that in the proband. CONCLUSIONS: We describe the spectrum of ATP7B mutations including 11 novel mutations in Indian WD patients and document lack of a single dominant mutation. Identical WD phenotype among siblings in only 6 of 8 families with >1 child affected by WD suggests that factors other than ATP7B mutations influence WD phenotype. 相似文献
18.
Kumar SK Dingli D Lacy MQ Dispenzieri A Hayman SR Buadi FK Rajkumar SV Litzow MR Gertz MA 《British journal of haematology》2008,141(2):205-211
A third of patients with multiple myeloma (MM) have a preceding diagnosis of plasma cell proliferative disorder (PCPD), mostly monoclonal gammopathy of undetermined significance (MGUS), smoldering MM (SMM) or plasmacytoma. While autologous stem cell transplantation (SCT) improves survival in MM, it is not clear if patients with preceding PCPD have a different outcome. We identified 151 patients with preceding PCPD from among 804 patients undergoing SCT, and their outcomes were compared. The response rates, including complete responses, were similar between the groups. Patients with a preceding diagnosis of MGUS had longer time to progression (TTP; 27·5 months vs. 17·2 months, P = 0·01), and longer overall survival (OS) from transplant (80·2 months vs. 48·3 months, P = 0·03) compared to those with de novo myeloma. However no differences were seen among those with a preceding diagnosis of SMM or plasmacytoma in terms of TTP or OS from transplant when compared to those with de novo myeloma. Multivariate analysis indicated that the presence of MGUS prior to myeloma was prognostic for post-transplant relapse independent of other known risk factors. Patients with pre-existing MGUS prior to myeloma diagnosis have a better outcome following HDT, reflecting more indolent disease and a favourable biology than those presenting with de novo myeloma. 相似文献
19.
Menon SC Ackerman MJ Cetta F O'Leary PW Eidem BW 《The American journal of cardiology》2008,102(10):1390-1393
Left atrial (LA) enlargement is an indicator of chronic elevation in left ventricular (LV) end-diastolic pressure as well as diastolic dysfunction. There is a lack of data on the significance of LA volume in the pediatric population. The objective of this study was to elucidate the relation between LA volume and diastolic dysfunction, clinical symptoms, and exercise capacity in young patients with hypertrophic cardiomyopathy. All patients aged <20 years with obstructive hypertrophic cardiomyopathy who underwent evaluation at the Mayo Clinic from 2002 to 2006 were retrospectively identified. Reviews of the LA volume index and other traditional diastolic Doppler echocardiographic parameters, as well as clinical data, were performed. A total of 88 patients (66 male) were studied. The median age at evaluation was 14 years. The mean LA volume index was 39 +/- 19 ml/m(2). Additional echocardiographic parameters included a mean LV outflow gradient of 55 +/- 51 mm Hg, a mean E/E' ratio of 14.0 +/- 7.6, and a mean maximal septal wall thickness of 23 +/- 9 mm. On univariate linear regression analysis, LA volume index had an excellent correlation with diastolic dysfunction grade (p <0.001, r(2) = 0.6), LV outflow tract gradient, mitral E/E', and the degree of mitral regurgitation. LA volume index was also positively associated with symptom score (p = 0.005) and maximal oxygen consumption on exercise test (n = 22; p = 0.01). On multivariate analysis, LA volume index was related to diastolic dysfunction grade (p <0.001) and mean mitral regurgitation grade (p = 0.05). In conclusion, this study demonstrates the potential clinical importance of LA volume index in pediatric hypertrophic cardiomyopathy as a marker of the severity of underlying diastolic dysfunction, symptom score, and decreased exercise capacity. LA volume index has significant diagnostic and prognostic value in these patients. 相似文献
20.
Shaji C. Menon MD Donald J. Hagler MD Frank Cetta MD Allison K. Cabalka MD 《Catheterization and cardiovascular interventions》2008,71(2):237-243
Acute thrombosis of the pulmonary arteries (PA) can occur during operative or catheter based interventions. This may have serious consequences especially in patients with palliated single ventricle physiology. Traditional therapy for PA thrombosis includes use of local or systemic thrombolytic therapy and surgical thrombectomy. Percutaneous transcatheter mechanical thrombectomy can be broadly divided into three categories based on their mechanisms of action: (a) mechanical fragmentation of the embolus using guide‐wires, pigtail catheters, or balloons (flossing technique), (b) extraction using cup or basket devices, or (c) hydrodynamic fragmentation and aspiration of the embolus. Rheolytic thrombectomy using AngioJet system (Possis Medical, Minneapolis, MN) uses hydrodynamic thrombus fragmentation and aspiration technique, and provides an alternative solution in management of acute thrombosis. We report three patients with complex congenital heart disease of single ventricle physiology palliated by cavopulmonary anastomosis or central shunts and PA thrombosis treated with AngioJet system. © 2008 Wiley‐Liss, Inc. 相似文献