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   2517篇
  免费   132篇
  国内免费   41篇
儿科学   15篇
妇产科学   16篇
基础医学   357篇
口腔科学   5篇
临床医学   348篇
内科学   496篇
皮肤病学   1篇
特种医学   41篇
外科学   19篇
综合类   513篇
预防医学   664篇
药学   128篇
中国医学   57篇
肿瘤学   30篇
  2024年   1篇
  2023年   28篇
  2022年   33篇
  2021年   42篇
  2020年   62篇
  2019年   79篇
  2018年   37篇
  2017年   53篇
  2016年   31篇
  2015年   49篇
  2014年   105篇
  2013年   96篇
  2012年   95篇
  2011年   130篇
  2010年   149篇
  2009年   163篇
  2008年   101篇
  2007年   172篇
  2006年   139篇
  2005年   116篇
  2004年   103篇
  2003年   121篇
  2002年   109篇
  2001年   70篇
  2000年   82篇
  1999年   60篇
  1998年   46篇
  1997年   44篇
  1996年   35篇
  1995年   31篇
  1994年   32篇
  1993年   25篇
  1992年   36篇
  1991年   27篇
  1990年   34篇
  1989年   31篇
  1988年   21篇
  1987年   21篇
  1986年   17篇
  1985年   14篇
  1984年   6篇
  1983年   4篇
  1982年   7篇
  1981年   5篇
  1980年   7篇
  1979年   8篇
  1978年   5篇
  1977年   7篇
  1976年   1篇
排序方式: 共有2690条查询结果,搜索用时 187 毫秒
1.
Introduction and ObjectivesHepatitis B surface antigen (HBsAg) clearance, indicating functional cure or resolved chronic hepatitis B (CHB), remains difficult to achieve via nucleos(t)ide analogue monotherapy. We investigated whether metformin add-on therapy could help achieve this goal in entecavir-treated patients with hepatitis B e antigen (HBeAg)-negative CHB.Patients and MethodsPatients with HBeAg-negative CHB who met eligibility criteria (entecavir treatment for > 12 months, HBsAg < 1000 IU/mL) were randomly assigned (1:1) to receive 24 weeks of either metformin (1000 mg, oral, once a day) or placebo (oral, once a day) add-on therapy. The group allocation was blinded for both patients and investigators. Efficacy and safety analyses were based on the intention-to-treat set. The primary outcome, serum HBsAg level (IU/mL) at weeks 24 and 36, was analysed using mixed models.ResultsSixty eligible patients were randomly assigned to the metformin (n = 29) and placebo (n = 31) groups. There was no substantial between-group difference in the HBsAg level at week 24 (adjusted mean difference 0.05, 95% confidence interval -0.04 to 0.13, p = 0.278) or week 36 (0.06, -0.03 to 0.15, p = 0.187), and no significant effect of group-by-time interaction on the HBsAg level throughout the trial (p = 0.814). The occurrence of total adverse events between the two groups was comparable (9 [31.0%] of 29 vs. 5 [16.1%] of 31, p = 0.227) and no patient experienced serious adverse events during the study.ConclusionAlthough it was safe, metformin add-on therapy did not accelerate HBsAg clearance in entecavir-treated patients with HBeAg-negative CHB.  相似文献   
2.
目的 探讨血清B细胞活化因子(BAFF)预测聚乙二醇干扰素-α(Peg-IFN-α)治疗非活动性HBsAg携带者(IHCs)临床治愈的效能。方法 2018年1月~2020年8月我院诊治的IHCs 54例,给予Peg-IFN-α治疗48 w,再随访24 w。采用ELISA法检测血清BAFF,应用Logistic回归分析影响临床治愈的因素,应用受试者工作特征曲线(ROC)及其曲线下面积(AUC)评价血清BAFF预测临床治愈的效能。结果 在72 w末,24例(44.4%)患者获得临床治愈,30例未获得临床治愈;治愈组与未治愈组基线血清BAFF水平分别为(670.9±105.9)pg/mL和(612.7±183.8)pg/mL,差异无统计学意义(P>0.05);在治疗12 w和24 w时,治愈组血清BAFF水平分别为(805.8±197.6)pg/mL和(895.3±227.4)pg/mL,显著高于未治愈组【分别为(675.3±190.8)pg/mL和(724.4±218.0)pg/mL,P 均<0.05】;多因素Logistic回归分析显示基线HBsAg定量、HBV DNA<20 IU/mL、治疗12 w和24 w时血清BAFF水平是影响临床治愈的独立因素;ROC分析显示,以Peg-IFN-α治疗12 w时血清BAFF水平大于704.3 pg/mL为截断点,其预测治疗应答的AUC=0.722, 敏感度为79.2%,特异度为66.7%,以24 w时血清BAFF水平大于741.9 pg/mL为截断点,其预测治疗应答的AUC=0.725,敏感度为75.0%,特异度为70.0%。结论 应用Peg-IFN-α治疗IHCs可获得约40%的应答率,在治疗过程中监测血清BAFF水平逐渐升高的患者可能获得满意的治疗结果。  相似文献   
3.
目的 分析2005-2019年江苏省抗病毒治疗的HIV/AIDS的HBV感染情况。方法 采用回顾性资料分析,研究对象来源于中国疾病预防控制信息系统艾滋病防治基本信息系统江苏省2005-2019年HIV/AIDS首次入组抗病毒治疗数据库,采用SPSS 16.0软件进行统计学分析。分析不同特征HIV/AIDS的HBsAg检测率和HBsAg阳性率的差异及其影响因素,单因素分析采用χ2检验,多因素分析采用非条件logistic回归模型。结果 2005-2019年江苏省首次入组抗病毒治疗的HIV/AIDS共29 288例,总体HBsAg检测率为49.8%(14 594/29 288),2005-2019年HBsAg检测率由0.0%(0/80)增加到75.2%(3 448/4 586),呈逐年上升趋势。进行HBsAg检测的HIV/AIDS中,江苏省籍占81.6%(11 915/14 594),男女性别比7.34:1(12 845:1 749),年龄(38.5±13.8)岁,汉族占96.1%(14 023/14 594),已婚/同居占48.9%(7 131/14 594)。男男性传播和异性性传播感染途径占97.9%(14 294/14 594)。logistic回归分析结果显示,HBsAg检测率的影响因素中,2015年及以后入组、外省户籍、已婚/同居、大专及以上文化程度、注射吸毒感染途径的人群HBsAg检测率较高。HIV/AIDS的HBsAg阳性率为8.6%(95%CI:8.2%~9.1%),HBsAg阳性率在2016年之前均>10.0%,自2016年以后稳定在6.7%~8.2%。HBsAg阳性率的影响因素中,2015年及以后入组、女性、年龄>59岁、大专及以上学历人群的HBsAg阳性率较低,而45~59岁年龄组和少数民族人群的HBsAg阳性率较高。结论 2005-2019年江苏省首次入组抗病毒治疗的HIV/AIDS中,HBsAg检测率总体不高,合并HBV感染高于一般人群,需要加强其HBsAg相关检测工作。  相似文献   
4.
5.
6.
Objective Pegylated-interferon monotherapy is the standard treatment for patients with chronic hepatitis B; however, the factors associated with its therapeutic effects remain unclear. Methods Patients with chronic hepatitis B were treated with pegylated interferon α-2a for 48 weeks. We evaluated the kinetics of hepatitis B surface antigen (HBsAg) during treatment and follow-up periods and the factors associated with an HBsAg response (defined as a change in HBsAg of ≥-1 log IU/mL from baseline). Results The study population comprised 50 patients. The median baseline levels of hepatitis B virus DNA and HBsAg were 5.00 and 3.40 log IU/mL. The median values of HBsAg reduction from baseline were -0.44 (n=48), -0.41 (n=40), and -0.68 (n=11) log IU/mL at the end of treatment and at 48 and 144 weeks post-treatment, respectively. The rates of HBsAg response were 24.0% and 22.5% at the end of treatment and at 48 weeks post-treatment, respectively. A multivariate analysis identified HBsAg <3.00 log IU/mL as an independent baseline factor contributing to the HBsAg response at the end of treatment and 48 weeks post-treatment (p=1.07×10-2 and 4.42×10-2, respectively). There were significant differences in the reduction of the HBsAg levels at 12 weeks of treatment and in the incidence of serum ALT increase during treatment between patients with and without an HBsAg response. Conclusion These findings suggest that the baseline HBsAg level, HBsAg kinetics at 12 weeks of treatment, and ALT increase during treatment are important factors contributing to the HBsAg response in pegylated interferon α-2a monotherapy for patients with chronic hepatitis B.  相似文献   
7.
Hepatitis B virus (HBV) infection continues to be a major public health issue worldwide. HBsAg loss is associated with functional remission and improved long‐term outcome, and is considered to be a ‘functional cure’ (also referred to as clinical or immunologic cure) for chronic hepatitis B. This ideal goal of therapy can be achieved using optimized combination regimens with direct‐acting antivirals [eg nucleos(t)ide analogues (NAs)] and immunomodulators [eg pegylated interferon alpha2a (Peg‐IFN)] in selected patients with chronic hepatitis B. Among different combination therapies currently available, those with NA lead‐in followed by Peg‐IFN in virally suppressed patients has been demonstrated to be effective. This review provides an updated overview of the evidence supporting the use of combination therapies and summarizes expert consensus on the roadmap to attain functional cure for chronic hepatitis B patients.  相似文献   
8.
Chronic hepatitis B virus (HBV) infection (CHB) in children remains a public health challenge despite significant success in programme is established to prevent mother‐to‐child transmission. In particular, CHB in Chinese children are mostly acquired through vertical transmission, which differs from the common infection route reported in other countries and regions. This situation has resulted in a high endemic prevalence of CHB in Chinese adults. Thus, successful treatment of children with CHB will prevent the development of advanced liver diseases in late adulthood. However, there is still no consensus on the clinical guideline to treat paediatric CHB. In this study, we evaluated the potential of interferon alpha (IFNa) treatment for Chinese children with CHB. A total of 41 patients with CHB aged 3‐17 years were enrolled in this retrospective study: 21 patients were treated with pegylated (PEG)‐IFNa and 20 patients without treatment served as the control group. The rates of HBV DNA suppression, hepatitis B e antigen (HBeAg) clearance and hepatitis B surface antigen (HBsAg) clearance were significantly higher in the PEG‐IFNa treatment group than in the control group (P < 0.05 at 48 weeks). Unexpectedly, PEG‐IFNa treatment achieved a high rate of HBsAb production, far exceeding the clinical outcome in documented PEG‐IFNa‐treated CHB adults. Further analysis revealed that younger children (3‐6 years old) were more responsive to PEG‐IFNa treatment with respect to achieving a protective level of HBsAb in a short treatment cycle than adolescents (10‐17 years old). Overall, these results indicate that the immune system of children might have a preserved PEG‐IFNa‐mediated mechanism to completely control HBV, which can help to design new strategies to treat CHB patients.  相似文献   
9.
Serum hepatitis B virus (HBV) RNA has emerged as a novel biomarker of treatment response. This study aimed to investigate the role of this marker in predicting long‐term outcome of patients with hepatitis B e antigen (HBeAg)‐negative chronic hepatitis B (CHB) receiving pegylated interferon (PEG‐IFN)‐based therapy. Serial serum samples from 91 patients with HBeAg‐negative CHB previously treated with PEG‐IFN alone or combined with entecavir in a randomized trial were retrospectively analysed. HBV RNA quantification was examined by droplet digital PCR. At the end of 3 years post‐treatment follow‐up, maintained virological response (MVR, HBV DNA < 2000 IU/mL), and hepatitis B surface antigen (HBsAg) clearance were achieved in 37.4% (34/91) and 7.7% (7/91), respectively. Baseline serum HBV RNA concentrations correlated with HBV DNA and covalently closed circular DNA but did not correlate with HBsAg levels. Multiple regression analysis showed that pre‐treatment HBV RNA and HBsAg were independently associated with MVR and HBsAg clearance. Baseline HBV RNA (cut‐off 2.0 log10 copies/mL) had a positive predictive value (PPV) and a negative predictive value in predicting MVR of 80.8% and 80.0%, respectively. At the same cut‐off value, PPV and NPV for predicting HBsAg clearance were 30.8% and 95.4%, respectively. At week 12 during therapy, HBV RNA level ≥ 2 log10 copies/mL displayed high NPVs of achieving MVR and HBsAg clearance (95% and 100%, respectively). In conclusion, the measurement of HBV RNA prior to PEG‐IFN‐based therapy could identify patients with high probability of MVR. In addition, HBV RNA kinetics may serve as a promising “stopping rule” in patients infected with HBV genotypes B or C.  相似文献   
10.
The discrimination between active chronic hepatitis B (CHB) and the clinically quiescent infection (CIB) is not always easy, as a significant portion of patients falls in a “grey” zone. Hepatitis B core‐related antigen (HBcrAg) is a now quantifiable serological marker with potential applications in diagnosis and therapy monitoring. The aim of the present study was to evaluate the HBcrAg serum levels in HBeAg‐negative HBV infection, and its ability in identifying the clinical profile, in comparison with HBsAg serum levels. HBcrAg was retrospectively assessed on serum samples from a population of treatment‐naive HBeAg‐negative patients by ChemiLuminescent Enzyme Immunoassay (CLEIA). HBsAg and HBV‐DNA data were collected. Serological data were associated to clinical profile, defined in the subsequent follow‐up of at least 1 year. In the overall population of 160 HBeAg‐negative patients, HBcrAg results weakly correlated with qHBsAg levels (Spearman r = 0.471, < 0.0001) and correlated closely with HBV‐DNA (Spearman r = 0.746, P < 0.0001). HBcrAg levels were significantly higher in 85 CHB patients relative to 75 CIB carriers. A value of 2.5 logU/mL produced the optimal cut‐off to identify CIB patients, with diagnostic accuracy comparable to HBsAg levels. In long‐term clinical evaluation, a single measurement of HBcrAg at the established cut‐off was optimally consistent with clinical outcome. Conversely, the HBsAg cut‐off performed well in the true quiescent phase and less in more difficult‐to‐categorize patients. In conclusion, single‐point use of HBcrAg serum levels provides an accurate identification of CIB and represents a useful tool for patient classification.  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