首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   232篇
  免费   20篇
  国内免费   5篇
耳鼻咽喉   1篇
儿科学   4篇
妇产科学   9篇
基础医学   29篇
口腔科学   6篇
临床医学   17篇
内科学   33篇
皮肤病学   5篇
神经病学   6篇
特种医学   4篇
外科学   34篇
综合类   14篇
预防医学   38篇
眼科学   6篇
药学   16篇
中国医学   1篇
肿瘤学   34篇
  2023年   8篇
  2022年   8篇
  2021年   11篇
  2020年   11篇
  2019年   34篇
  2018年   24篇
  2017年   17篇
  2016年   10篇
  2015年   7篇
  2014年   13篇
  2013年   12篇
  2012年   10篇
  2011年   8篇
  2010年   8篇
  2009年   4篇
  2008年   5篇
  2007年   6篇
  2006年   5篇
  2005年   7篇
  2004年   2篇
  2003年   5篇
  2002年   1篇
  1998年   2篇
  1996年   1篇
  1994年   1篇
  1988年   2篇
  1985年   3篇
  1984年   2篇
  1983年   4篇
  1982年   4篇
  1981年   3篇
  1980年   2篇
  1979年   3篇
  1978年   2篇
  1977年   2篇
  1976年   6篇
  1975年   1篇
  1974年   1篇
  1973年   2篇
排序方式: 共有257条查询结果,搜索用时 15 毫秒
1.
《Vaccine》2022,40(12):1872-1878
BackgroundThe MenB-FHbp vaccine (Trumenba®) is licensed in various countries for the prevention of meningococcal serogroup B disease in individuals ≥ 10 years of age. The clinical development program included 11 completed trials where, in each trial, MenB-FHbp had an acceptable safety profile after a primary vaccination series was administered to individuals 10–65 years of age. However, the detection of potential rare events was limited because of individual clinical trial size. The current safety analysis evaluates pooled reactogenicity and other adverse events (AEs) reported in these trials to identify new safety signals not detectable in individual trials.MethodsEleven trials contributed safety data, of which 10 recorded local and systemic reactogenicity events; 8 of the trials were controlled, and reactogenicity data were pooled for 7 of these 8 trials. Additional AE evaluations included immediate AEs (IAEs), medically attended AEs (MAEs), serious AEs (SAEs), newly diagnosed chronic medical conditions (NDCMCs), and autoimmune or neuroinflammatory conditions.ResultsLocal and systemic reactions were more frequent in the MenB-FHbp group (n = 15,294) compared with controls (n = 5509), although most reactions were transient and mild to moderate in severity. Frequencies of IAEs, SAEs, MAEs, NDCMCs, and autoimmune or neuroinflammatory conditions were similar between the MenB-FHbp and control groups.ConclusionsMenB-FHbp demonstrated a favorable safety and tolerability profile in the clinical development program of > 15,000 vaccine recipients ≥ 10 years of age. No new safety signals were identified in the pooled analysis compared with data from the individual trials. Continued postmarketing safety surveillance is important for the identification of rare events.Clinicaltrials.gov: NCT01299480; NCT000808028; NCT00879814; NCT00780806; NCT01352845; NCT01352793; NCT01461993; NCT01323270; NCT01830855; NCT01461980; NCT01768117.  相似文献   
2.
3.
4.
Mammalian CEP55 (centrosomal protein 55 kDa) is a coiled‐coil protein localized to the centrosome in interphase cells and is required for cytokinesis. A homozygous non‐sense mutation in human CEP55 has been recently identified in perinatal lethal MARCH (multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia and hydranencephaly) syndrome. We have isolated zebrafish cep55 mutants defective in head morphology. The zebrafish cep55 gene was expressed in the head including the retina and the pectoral fin at 1 day post‐fertilization (dpf), and extensive cell death was widely observed in the head and tail of the cep55 mutant. In the cep55 mutant, the anterior–posterior distance of the ventral pharyngeal arches was short, and retinal lamination was disorganized. Neural cells, such as islet1‐positive cells and pax2‐positive cells, and fli1b‐positive vascular cells were reduced in the head of the cep55 mutant. Thus, we propose that the zebrafish cep55 mutant is a model organism for human MARCH syndrome.  相似文献   
5.

Background

Undifferentiated-type early gastric cancers account for a large proportion of gastric cancers in younger patients. Therefore, the clinical outcomes of endoscopic resection in younger patients are a major concern. We aimed to investigate the influence of age on lymph node metastasis and long-term survival after surgery for undifferentiated-type early gastric cancers.

Methods

We identified 4,236 patients who underwent surgery for undifferentiated-type early gastric cancers. For each T stage, the correlation between age and lymph node metastasis was analyzed using a multivariate logistic regression. Lymph node metastasis rates were compared between younger (<40 years) and older patients (≥40 years) who fulfilled the expanded criteria for endoscopic resection. The Kaplan–Meier method was used to compare long-term survival between younger and older patients.

Results

Younger age groups (20–29 and 30–39 years) had the highest lymph node metastasis rate within each T stage (5.7% and 5.7% for T1a, 26.3% and 24.1% for T1b, respectively). After adjusting for possible covariates, however, age did not have a significant effect on lymph node metastasis in either T stage (P?=?.127 for T1a, P?=?.114 for T1b). Among patients fulfilling the expanded indication for endoscopic resection, younger patients had a slightly higher lymph node metastasis rate compared with older patients (2.7% versus 2.0%), although this difference was not statistically significant. Although younger patients had a significantly better overall survival (P < .001), no significant age-related differences were observed in recurrence-free and disease-specific survival (P?=?.051 and P?=?.069)

Conclusion

Endoscopic resection may be feasible in young patients with undifferentiated-type early gastric cancers because these patients share a similar lymph node metastasis rate and long-term survival outcomes with older patients.  相似文献   
6.

Background

The significance of FMS-like tyrosine kinase 3 (FLT3)-ITD mutation in acute myeloid leukemia (AML) prognosis has been well established. The aims of this study were to investigate the prognostic impact of the FLT3 protein (CD135) expression and its association with FLT3-ITD mutation, and to identify its role in minimal residual disease.

Patients and Methods

CD135 was measured by flow cytometry on leukemic blasts of 257 adults with de novo AML. High expression of CD135 ≥ 20% was correlated with clinical, laboratory, and other prognostic factors that influenced treatment outcome. FLT3-ITD mutation was tested by PCR.

Results

The frequency of CD135 expression was 138 (53.7%) of 257. FLT3-ITD was detected in (21.4%). Positive CD135 expression was associated with high total leukocyte count (P = .006), platelet count (P = .003), monocytic leukemia (P < .001), and CD34 (P = .008) and CD117 (P = .006) expression. CD135 expression ≥ 25% was a predictor of FLT3-ITD mutation (P = .03). CD135 overexpression was a negative predictor of complete remission and of postinduction minimal residual disease at days 14 and 28 (P < .001). CD135 had an adverse impact on overall and disease-free survival (68.5% vs. 15%, P = .002). Multivariate analysis indicated CD135 was the sole independent prognostic factor for overall survival (hazard ratio = 2.49; 95% confidence interval, 1.855-3.345; P < .001).

Conclusion

CD135 is emerging as a prognostic factor, a new marker for minimal residual disease, and a potential novel therapeutic target of AML.  相似文献   
7.

Background

We sought to determine the 10-year survivorship of single-radius, posterior-stabilized total knee arthroplasty (TKA) in Asian patients. We also aimed to determine whether the long-term clinical and radiographic results differed between patients with and without patellar resurfacing.

Methods

This retrospective study included 148 (115 patients) consecutive single-radius, posterior-stabilized TKAs. Ten-year survivorship analysis was performed using the Kaplan–Meier method with additional surgery for any reason as the end-point. Furthermore, long-term clinical and radiographic results of 109 knees (74%; 84 patients) with more than 10-year follow-up were analyzed. Ten-year survivorship and long-term outcomes after surgery were determined, and outcomes were compared between patients with and without patellar resurfacing.

Results

The cumulative survival rate of the single-radius posterior-stabilized TKA of 148 knees was 97.7% (95% confidence interval, 93.1%–99.3%) at 10 years after surgery. Three knees required additional surgery during the 10-year follow-up because of one case of instability and two cases of periprosthetic infections. Mean postoperative Knee Society knee score and function score were 97 points and 75 points, respectively. There were no cases of aseptic loosening of the prosthesis, even though a non-progressive radiolucent line was found in 10 (9%) knees. There were no differences in postoperative scores and degree of patellar tilt and displacement between patients with and without patellar resurfacing.

Conclusions

Single-radius, posterior-stabilized TKA showed satisfactory long-term clinical and radiographic outcomes in Asian patients regardless of patellar resurfacing, with comparable survivorship to that reported in westerners.  相似文献   
8.
9.
10.
BackgroundNon-small cell lung cancer (NSCLC) chemoresistance usually limits the clinical efficacy of chemotherapeutic approaches. However, few reports have revealed the regulation of miR-135b and Frizzled-1 (FZD1) involved in NSCLC chemoresistance.MethodsTo identify the mechanism of miR-135b and FZD1 in NSCLC chemoresistance and to observe their biological functions, we detected the expression levels of miR-135b and FZD1 by conducting quantitative real-time polymerase chain reaction (RT-qPCR) and modified the expressions of miR-135b and FZD1 by transiently transfecting cells with miR-135b mimics or FZD1-siRNA. The 3′-untranslated region (3′-UTR) of FZD1 combined with miR-135b was verified through dual-luciferase reporter assay.ResultsCompared with that in A549 parental cell lines, the miR-135b expression in drug-resistant lung cancer cell lines (A549/DDP) was decreased and their FZD1 expression was increased. The increased miR-135b expression and silenced FZD1 expression enhanced the sensitivity of resistant cells to cisplatin treatment. The high expression of miR-135b in A549/DDP cells remarkably decreased the mRNA levels of FZD1. FZD1 was further identified as the functional downstream target of miR-135b by directly targeting the 3′-UTR of FZD1.ConclusionThe amplification of miR-135b suppressed NSCLC chemoresistance by directly mediating the FZD1 downregulation.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号