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First-line chemotherapy for advanced/metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric/gastroesophageal junction cancer (GC/GEJC) has poor median overall survival (OS; <1 year). We report efficacy and safety results from Chinese patients in the phase III global CheckMate 649 study of nivolumab plus chemotherapy vs chemotherapy for the first-line treatment of GC/GEJC/esophageal adenocarcinoma (EAC). Chinese patients with previously untreated advanced or metastatic GC/GEJC/EAC were randomized to receive nivolumab (360 mg Q3W or 240 mg Q2W) plus chemotherapy (XELOX [capecitabine and oxaliplatin] Q3W or FOLFOX [oxaliplatin, leucovorin and 5-fluorouracil] Q2W), nivolumab plus ipilimumab (not reported) or chemotherapy alone. OS, blinded independent central review-assessed progression-free survival (PFS), objective response rate (ORR), duration of response (DOR) and safety are reported. Of 1581 patients enrolled and randomized, 208 were Chinese. In these patients, nivolumab plus chemotherapy resulted in clinically meaningful improvement in median OS (14.3 vs 10.2 months; HR 0.61 [95% CI: 0.44-0.85]), median PFS (8.3 vs 5.6 months; HR 0.57 [95% CI: 0.40-0.80]), ORR (66% vs 45%) and median DOR (12.2 vs 5.6 months) vs chemotherapy, respectively. The safety profile was acceptable, with no new safety signals observed. Consistent with results from the global primary analysis of CheckMate 649, nivolumab plus chemotherapy demonstrated a clinically meaningful improvement in OS and PFS and higher response rate vs chemotherapy and an acceptable safety profile in Chinese patients. Nivolumab plus chemotherapy represents a new standard first-line treatment for Chinese patients with non-HER2-positive advanced GC/GEJC/EAC.  相似文献   
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We aim to assess the safety and efficacy of proxalutamide, a novel androgen receptor antagonist, for men with metastatic castration-resistant prostate cancer (mCRPC) in a multicenter, randomized, open-label, phase 2 trial. In our study, the enrolled mCRPC patients were randomized to 100, 200 and 300 mg dose groups at 1:1:1. The primary efficacy endpoint was prostate-specific antigen (PSA) response rate. The secondary endpoints included objective response rate (ORR), disease control rate (DCR) and time to PSA and radiographic progression. Safety and pharmacokinetics were also assessed. Finally, there were 108 patients from 17 centers being enrolled. By week 16, there were 13 (35.1%), 12 (36.4%) and 15 (42.9%) patients with confirmed 50% or greater PSA decline in 100 mg (n = 37), 200 mg (n = 33) and 300 mg (n = 35) groups, respectively. Among the 19 patients with target lesions at study entry, three (15.8%) had a partial response and 12 (63.2%) had stable disease. The ORRs of 20.0%, 22.2%, 0% and DCRs of 80.0%, 88.9%, 60.0% were, respectively, achieved in 100, 200 and 300 mg groups. By the maximum follow-up time of 24 weeks, there were 42.6% and 10.2% of cases experiencing PSA progression and radiographic progression, respectively. Overall, adverse events (AEs) were experienced by 94.4% of patients, most of which were mild or moderate. There were 28 patients experiencing ≥grade 3 AEs. The most common AEs were fatigue (17.6%), anemia (14.8%), elevated AST (14.8%) and ALT (13.0%), decreased appetite (13.0%). These findings preliminarily showed the promising antitumor activity of proxalutamide in patients with mCRPC with a manageable safety profile. The proxalutamide dose of 200 mg daily is recommended for future phase 3 trial (Clinical trial registration no. CTR20170177).  相似文献   
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既往左心耳内血栓是左心耳封堵的禁忌证。该文报道1例心房颤动患者, 有反复脑梗死病史, 合并糖尿病、肾功能不全及冠心病, 心脏CT血管成像诊断左心耳血栓, 因抗凝治疗不耐受, 故行左心耳封堵术。术后予抗凝和/或抗血小板治疗仍反复发生器械相关血栓。提示心房颤动合并左心耳血栓患者应慎行左心耳封堵术, 术后需个体化调整抗栓方案、密切随诊。  相似文献   
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目的研究老年人群无症状脑小血管病(CSVD)的发生率、影像学特征及其影响因素。方法选取2019年10月至2020年8月在我院老年医学部门诊体检、既往无神经系统疾病病史的老年人共201例, 完善头颅磁共振成像(MRI)检查。采用脑小血管病总负担评分对腔隙灶、脑白质病变、脑微出血及血管周围间隙扩大共4种CSVD影像学特征进行总体评估, 记为0~4分。分析入组人群不同影像学特征分布情况, 并将CSVD总负担评分与其临床情况进行相关性分析。结果本研究中影像学符合CSVD共133例(66.2%)。其中, 腔隙灶44例(21.9%), 中-重度脑室旁白质病变(PVWMH)88例(43.8%), 中-重度深部脑白质病变(DWMH)30例(14.9%), 基底节区血管周围间隙扩大(EPVS)61例(30.3%), 脑微出血(CMB)92例(45.8%)。CSVD总负担评分(OR=1.876, 95%CI:1.045~3.364, χ2=4.441, P=0.035)、PVWMH(OR=2.821, 95%CI:1.517~5.244, χ2=10.752, P=0.001)、DWMH(OR=2.130...  相似文献   
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Metabolic Brain Disease - Doxorubicin (DOX) is an effective anticancer drug, however, side effects such as cognitive impairment and cardiotoxicity have limited its clinical use. Juglanin (JUG) is a...  相似文献   
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Lim  Hui Fang  Tan  Nadia Suray  Dehghan  Roghayeh  Shen  Meixin  Liew  Mei Fong  Bee  Stella Wei Lee  Sia  Yee Yen  Liu  Jianjun  Khor  Chiea Chuen  Kwok  Immanuel  Ng  Lai Guan  Angeli  Veronique  Dorajoo  Rajkumar 《Lung》2022,200(3):401-407

Telomere attrition is an established ageing biomarker and shorter peripheral blood leukocyte telomere length has been associated with increased risks of respiratory diseases. However, whether telomere length in disease-relevant sputum immune cells of chronic respiratory disease patients is shortened and which pathways are dysfunctional are not clear. Here we measured telomere length from sputum samples of bronchiectasis and asthmatic subjects and determined that telomere length in sputum of bronchiectasis subjects was significantly shorter (Beta?=????1.167, PAdj?=?2.75?×?10?4). We further performed global gene expression analysis and identified genes involved in processes such as NLRP3 inflammasome activation and regulation of adaptive immune cells when bronchiectasis sputum telomere length was shortened. Our study provides insights on dysfunctions related to shortened telomere length in sputum immune cells of bronchiectasis patients.

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9.
目的评估CHA2DS2-VASc评分对急性心肌梗死(AMI)患者院内结局事件的预测价值。方法回顾性分析冠心病医疗结果评价和临床转化研究(China PEACE)回顾性急性心肌梗死研究中23728例AMI患者的病历信息,按CHA2DS2-VASc评分分为低(0~3分)、中(4~6分)、高(7~9分)分值组。院内结局包括主要不良心血管事件、死亡、死亡或放弃治疗、再发心肌梗死、缺血性卒中等。采用多因素Cox回归分析CHA2DS2-VASc评分对AMI患者院内结局的影响。通过受试者工作特征(ROC)曲线,评估CHA2DS2-VASc评分对AMI患者院内死亡与死亡或放弃治疗的预测价值。结果入组患者年龄66(56,75岁)岁,女性占30.7%。CHA2DS2-VASc评分高分值组患者院内结局事件发生率更高,基础疾病更多(P值均<0.001);多因素logistic回归中,院内病死率(OR=6.13,95%CI 4.77~7.87,P<0.001)、院内死亡或放弃治疗率(OR=6.43,95%CI 5.16~8.00,P<0.001)、主要心血管事件发生率(OR=4.94,95%CI 4.06~6.01,P<0.001)明显高于其他两组。ROC曲线分析显示,无论院内病死率,还是死亡或放弃治疗率,CHA2DS2-VASc评分与简化版全球急性冠状动脉事件登记(global registry of acute coronary events,mini-GRACE)评分相比差异无统计学意义(ROC曲线下面积:0.699与0.696,P=0.752;0.708与0.713,P=0.489)。结论CHA2DS2-VASc评分是一种有效预测AMI患者院内风险的评估工具,该评分操作简单,预测价值与mini-GRACE评分相当。  相似文献   
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吴俣  刘民 《中国全科医学》2022,25(11):1309-1313
从新型冠状病毒肺炎(COVID-19)疫情初始至今,COVID-19的病原体新型冠状病毒(SARS-CoV-2)不断进化和变异,产生传播力和毒力变化的变异株,如Alpha(B.1.1.7)、Beta(B.1.351)、Gamma(P.1)、Delta(B.1.617.2)以及Omicron(B.1.1.529)变异株。深入研究不同变异株感染所致的COVID-19潜伏期有助于追溯传染源,确定密切接触者的留验、检疫和医学观察期限,为及时调整COVID-19疫情防控措施提供依据。本文主要综述了国内外感染SARS-CoV-2野生株和不同变异株的COVID-19潜伏期的相关研究,研究发现,感染SARS-CoV-2野生株的潜伏期在4~8 d,中位潜伏期约为5.5 d。感染Beta、Gamma变异株的潜伏期与野生株基本类似,约为5 d。感染Alpha、Delta和Omicron变异株的潜伏期则低于其他毒株,分别为4 d、4 d和3 d。  相似文献   
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