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   1394篇
  免费   112篇
  国内免费   62篇
妇产科学   21篇
基础医学   19篇
口腔科学   1篇
临床医学   65篇
内科学   161篇
皮肤病学   2篇
特种医学   22篇
外国民族医学   1篇
外科学   79篇
综合类   222篇
预防医学   23篇
药学   248篇
中国医学   8篇
肿瘤学   696篇
  2023年   9篇
  2022年   21篇
  2021年   24篇
  2020年   29篇
  2019年   18篇
  2018年   24篇
  2017年   49篇
  2016年   45篇
  2015年   50篇
  2014年   140篇
  2013年   105篇
  2012年   139篇
  2011年   122篇
  2010年   105篇
  2009年   119篇
  2008年   139篇
  2007年   115篇
  2006年   95篇
  2005年   72篇
  2004年   53篇
  2003年   38篇
  2002年   15篇
  2001年   13篇
  2000年   13篇
  1999年   7篇
  1998年   2篇
  1997年   2篇
  1996年   4篇
  1992年   1篇
排序方式: 共有1568条查询结果,搜索用时 15 毫秒
1.
目的探讨经尿道膀胱肿瘤二次电切术(Re-TURBT)在降低Ta和T1期非肌层浸润性膀胱癌(NMIBC)电切术后肿瘤复发率的临床价值。 方法回顾性分析2015年2月至2018年11月我院86例诊断为Ta和T1期的NMIBC患者。患者接受单次经尿道膀胱肿瘤电切术为对照组(40例),接受二次经尿道膀胱肿瘤切除术为观察组(46例),两组患者首次电切术中均联合了吉西他滨即刻膀胱灌注化疗。统计观察组二次电切的阳性率及肿瘤分期分级变化情况,同时比较两组患者术后2年内的肿瘤复发及进展情况。 结果两组患者年龄、性别、吸烟史、肿瘤最大径、肿瘤个数、首次电切病理分期比较差异无统计学意义(P>0.05)。观察组二次电切术后的病理结果显示,11例(23.91%)检出残余癌,5例出现临床分期升级,4例病理分级升级。观察组术后2年总复发率低于对照组(P<0.05)。两组术后2年总进展率差异无统计学意义(P>0.05)。 结论Re-TURBT可明显降低Ta和T1期NMIBC电切术后肿瘤复发率,同时可获得更准确的肿瘤分期,具有一定的临床价值。  相似文献   
2.
《Pancreatology》2022,22(8):1159-1166
Background/objectivesPancreatic adenosquamous carcinoma (PASC) is a rare variant of pancreatic ductal adenocarcinoma (PDAC). The usual treatment for metastatic or recurrent PASC is systemic chemotherapy in accordance with the PDAC treatment strategy. This study aimed to investigate the efficacy of chemotherapy, especially the benefit of recent combination therapies, in patients with metastatic or recurrent PASC.MethodsWe conducted a multicenter retrospective analysis of 116 patients with metastatic or recurrent PASC treated with first-line chemotherapy between April 2001 and December 2017 at 24 Japanese institutions.ResultsCombination chemotherapies included gemcitabine + nab-paclitaxel (GnP, n = 28), fluorouracil/leucovorin + irinotecan + oxaliplatin (FFX, n = 10), gemcitabine + S-1 (GS, n = 10), and others (n = 9). Monotherapies included gemcitabine (n = 51) and S-1 (n = 8). The median overall survival (OS) was 6.5, 7.3, and 4.3 months for the whole cohort, the combination therapy group, and the monotherapy group, respectively. Multivariate analysis indicated that combination therapy showed a better trend in OS than monotherapy (hazard ratio = 0.68; 95% confidence interval, 0.38–1.20). GnP or FFX were selected in 58.7% of patients after FFX was approved in Japan, and revealed a median OS, median progression-free survival, and objective response rate of 7.3 months, 2.8 months, and 26.9% in GnP and 7.2 months, 2.3 months, and 20.0% in FFX respectively.ConclusionsThis study suggests that combination therapy may be more effective than monotherapy. GnP and FFX showed similar and clinically meaningful efficacy for patients with metastatic or recurrent PASC.  相似文献   
3.
4.
5.
The prognosis of pancreatic cancer is poor with the overall 5-year survival rate of less than 5% changing minimally over the past decades and future projections predicting it developing into the second leading cause of cancer related mortality within the next decade. Investigations into the mechanisms of pancreatic cancer development, progression and acquired chemoresistance have been constant for the past few decades, thus resulting in the identification of human nucleoside transporters and factors affecting cytotoxic uptake via said transporters. This review summaries the aberrant expression and role of human nucleoside transports in pancreatic cancer, more specifically human equilibrative nucleoside transporter 1/2 (hENT1, hENT2), and human concentrative nucleoside transporter 1/3 (hCNT1, hCNT3), while briefly discussing the connection and importance between these nucleoside transporters and mucins that have also been identified as being aberrantly expressed in pancreatic cancer. The review also discusses the incidence, current diagnostic techniques as well as the current therapeutic treatments for pancreatic cancer. Furthermore, we address the importance of chemoresistance in nucleoside analogue drugs, in particular, gemcitabine and we discuss prospective therapeutic treatments and strategies for overcoming acquired chemoresistance in pancreatic cancer by the enhancement of human nucleoside transporters as well as the potential targeting of mucins using a combination of mucolytic compounds with cytotoxic agents.  相似文献   
6.
《Pancreatology》2021,21(6):1064-1070
BackgroundThe efficacy and safety of gemcitabine and nab-paclitaxel (GnP) among elderly patients with advanced pancreatic ductal adenocarcinoma (PDAC) remains poorly understood. We aimed to evaluate the safety and efficacy of GnP in this setting.Patients and methodsWe retrospectively included all consecutive patients aged ≥65 years with histologically proven PDAC who received at least one cycle of GnP (January 2014 to May 2018) in four academic centers. The primary endpoints were toxicity and overall survival (OS). Secondary endpoints were progression-free survival (PFS) and objective response rate. We compared patients aged ≥ or <75 years.ResultsThe study included 127 patients; among them 42 (33.1%) were aged ≥ 75 years. Fifty-seven and seventy patients received GnP as the first-line and the second-line treatment or beyond, respectively. Sixty-seven patients had at least one grade 3/4 adverse event, the most frequent being neutropenia and peripheral neuropathy. No deaths were related to toxicity. OS (median, 8.0 months; 95% confidence interval (CI), 5.8–10.2) and PFS (median, 5.5 months; 95% CI, 4.8–6.2) were similar for patients aged <75 or ≥75 years in the whole cohort and among patients receiving GnP as the first-line treatment. Cephalic PDAC, liver metastases, hypoalbuminemia, and GnP received beyond the first-line were associated with a significantly shorter OS on the multivariate analysis.ConclusionGnP is well tolerated and effective in elderly patients with advanced PDAC, even patients aged ≥75 years. The data from daily clinical practice are consistent with the results reported with first-line treatment and highlight the relevance of GnP administration in elderly patients.  相似文献   
7.
In spite of recent diagnostic and therapeutic advances, the prognosis of pancreatic ductal adenocarcinoma (PDAC) remains very poor. As most patients are not amenable to curative intent treatments, optimized palliative management is highly needed. One key question is to what extent promising results produced by randomized controlled trials (RCTs) correspond to clinically meaningful outcomes in patients treated outside the strict frames of a clinical trial. To answer such questions, real-world evidence is necessary. The present paper reviews and discusses the current literature on first- and second-line palliative chemotherapy in PDAC. Notably, a growing number of studies report that the outcomes of the two predominant first-line multidrug regimens, i.e. gemcitabine plus nab-paclitaxel (GnP) and folfirinox (FFX), is similar in RCTs and real-life populations. Outcomes of second-line therapy following failure of first-line regimens are still dismal, and considerable uncertainty of the optimal management remains. Additional RCTs and real-world evidence studies focusing on the optimal treatment sequence, such as FFX followed by GnP or vice versa, are urgently needed. Finally, the review highlights the need for prognostic and predictive biomarkers to inform clinical decision making and enable personalized management in advanced PDAC.  相似文献   
8.
Glutathione-S-transferases (GSTs) not only show cytoprotective role and their involvement in the development of anticancer drug resistance, but also transmit signals that control cell proliferation and apoptosis. However, the role of GST isoforms in chemotherapy resistance remains elusive in pancreatic cancer. Here, we demonstrated that gemcitabine treatment increased the GSTM2 expression in pancreatic cancer cell lines. Knockdown of GSTM2 by siRNA elevated apoptosis and decreased viability of pancreatic cancer cells treated with gemcitabine. Moreover, in vivo experiments further showed that shRNA induced GSTM2 downregulation enhanced drug sensitivity of gemcitabine in orthotopic pancreatic tumor mice. We also found that GSTM2 levels were lower in tumor tissues than in non-tumor tissues and higher GSTM2 expression was significantly associated with longer overall survival. In conclusion, our findings indicate that GSTM2 expression is essential for the survival of pancreatic cancer cells undergoing gemcitabine treatment and leads to chemo resistance. Downregulation of GSTM2 in pancreatic cancer may benefit gemcitabine treatment. GSTM2 expression in patients also shows significant correlation with overall survival. Thus, our study suggests that GSTM2 is a potential target for chemotherapy optimization and prognostic biomarker of pancreatic cancer.  相似文献   
9.
Lung cancer is the most widespread type of cancer and the primary cause of cancer-related death in the world. In this study, we aimed to analyze the cost-effectiveness of second-line chemotherapy strategies based on gemcitabine, pemetrexed, and docetaxel for advanced non-squamous non-small cell lung cancer patients in China.A Markov model based on three states, progression-free survival, progressed survival and death, was constructed to simulate the progression of the disease in a 6-year horizon. Sensitivity analysis was performed to evaluate the robustness of the model. The primary outcome of the model was the incremental cost-effectiveness ratio at a willingness-to-pay threshold of 3× per capita GDP of China in 2018 ($29 383). The baseline model results showed that the quality-adjusted life years over the course of the disease associated with second-line chemotherapy strategies were 0.233, 0.417 and 0.272 for gemcitabine, pemetrexed and docetaxel, respectively, and the corresponding total costs were $5321.02, $12 143.94, and $9479.42. Gemcitabine, pemetrexed and docetaxel resulted in the incremental cost-effectiveness ratios of $37 081.09 and $106 625.64 per quality-adjusted life year gained. The incremental cost-effectiveness ratio of pemetrexed and docetaxel compared with gemcitabine exceeded the willingness-to-pay threshold. One-way sensitivity analysis showed that the utility value of gemcitabine in the progressed survival state was the most influential parameter.  相似文献   
10.
BACKGROUND Effective endoscopic management is fundamental for the treatment of extrahepatic cholangiocarcinoma(ECC). However, current biliary stents that are widely used in clinical practice showed no antitumor effect. Drug-eluting stents(DESs) may achieve a combination of local chemotherapy and biliary drainage to prolong stent patency and improve prognosis.AIM To develop novel DESs coated with gemcitabine(GEM) and cisplatin(CIS)-coloaded nanofilms that can maintain the continuous and long-term release of antitumor agents in the bile duct to inhibit tumor growth and reduce systemic toxicity.METHODS Stents coated with different drug-eluting components were prepared by the mixed electrospinning method, with poly-L-lactide-caprolactone(PLCL) as the drug-loaded nanofiber membrane and GEM and/or CIS as the antitumor agents. Four different DESs were manufactured with four drug-loading ratios(5%, 10%, 15%, and 20%), including bare-loaded(PLCL-0), single-drug-loaded(PLCL-GEM and PLCL-CIS), and dual-drug-loaded(PLCL-GC) stents. The drug release property, antitumor activity, and biocompatibility were evaluated in vitro and in vivo to confirm the feasibility and efficacy of this novel DES for ECC.RESULTS The in vitro drug release study showed the stable, continuous release of both GEM and CIS, which was sustained for over 30 d without an obvious initial burst, and a higher drug-loaded content induced a lower release rate. The drug-loading ratio of 10% was used for further experiments due to its ideal inhibitory efficiency and relatively low toxicity. All drug-loaded nanofilms effectively inhibited the growth of EGI-1 cells in vitro and the tumor xenografts of nude mice in vivo; in addition, the dual-loaded nanofilm(PLCL-GC) had a significantly better effect than the single-drug-loaded nanofilms(P 0.05). No significant differences in the serological analysis(P 0.05) or histopathological changes were observed between the single-loaded and drug-loaded nanofilms after stent placement in the normal porcine biliary tract.CONCLUSION This novel PLCL-GEM and CIS-eluting stent maintains continuous, stable drug release locally and inhibits tumor growth effectively in vitro and in vivo. It can also be used safely in normal porcine bile ducts. We anticipate that it might be considered an alternative strategy for the palliative therapy of ECC patients.  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