收费全文 | 23588篇 |
免费 | 1864篇 |
国内免费 | 71篇 |
耳鼻咽喉 | 274篇 |
儿科学 | 771篇 |
妇产科学 | 577篇 |
基础医学 | 3498篇 |
口腔科学 | 319篇 |
临床医学 | 2409篇 |
内科学 | 4502篇 |
皮肤病学 | 394篇 |
神经病学 | 2450篇 |
特种医学 | 716篇 |
外科学 | 2988篇 |
综合类 | 619篇 |
现状与发展 | 1篇 |
一般理论 | 30篇 |
预防医学 | 2028篇 |
眼科学 | 650篇 |
药学 | 1579篇 |
1篇 | |
中国医学 | 42篇 |
肿瘤学 | 1675篇 |
2023年 | 149篇 |
2022年 | 290篇 |
2021年 | 601篇 |
2020年 | 345篇 |
2019年 | 514篇 |
2018年 | 626篇 |
2017年 | 417篇 |
2016年 | 488篇 |
2015年 | 598篇 |
2014年 | 759篇 |
2013年 | 1110篇 |
2012年 | 1497篇 |
2011年 | 1463篇 |
2010年 | 873篇 |
2009年 | 781篇 |
2008年 | 1314篇 |
2007年 | 1301篇 |
2006年 | 1202篇 |
2005年 | 1242篇 |
2004年 | 1250篇 |
2003年 | 1131篇 |
2002年 | 1009篇 |
2001年 | 372篇 |
2000年 | 360篇 |
1999年 | 348篇 |
1998年 | 247篇 |
1997年 | 185篇 |
1996年 | 192篇 |
1995年 | 187篇 |
1994年 | 147篇 |
1993年 | 171篇 |
1992年 | 253篇 |
1991年 | 227篇 |
1990年 | 241篇 |
1989年 | 241篇 |
1988年 | 221篇 |
1987年 | 197篇 |
1986年 | 203篇 |
1985年 | 228篇 |
1984年 | 179篇 |
1983年 | 144篇 |
1982年 | 156篇 |
1981年 | 155篇 |
1980年 | 138篇 |
1979年 | 118篇 |
1977年 | 100篇 |
1976年 | 119篇 |
1975年 | 107篇 |
1974年 | 142篇 |
1973年 | 101篇 |
Introduction
In the phase II/III KEYNOTE-010 study (ClinicalTrials.gov, NCT01905657), pembrolizumab significantly prolonged overall survival over docetaxel in patients with previously treated, programmed death ligand 1–expressing (tumor proportion score ≥ 1%), advanced NSCLC. Health-related quality of life (HRQoL) results are reported here.Methods
Patients were randomized 1:1:1 to pembrolizumab 2 or 10 mg/kg every 3 weeks or docetaxel 75 mg/m2 every 3 weeks. HRQoL was assessed using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLC) Core 30 (C30), EORTC QLQ–Lung Cancer 13 (LC13), and EuroQoL-5D. Key analyses included mean baseline-to-week-12 change in global health status (GHS)/quality of life (QoL) score, functioning and symptom domains, and time to deterioration in a QLQ-LC13 composite endpoint of cough, dyspnea, and chest pain.Results
Patient reported outcomes compliance was high across all three instruments. Pembrolizumab was associated with better QLQ-C30 GHS/QoL scores from baseline to 12 weeks than docetaxel, regardless of pembrolizumab dose or tumor proportion score status (not significant). Compared with docetaxel, fewer pembrolizumab-treated patients had “deteriorated” status and more had “improved” status in GHS/QoL. Nominally significant improvement was reported in many EORTC symptom domains with pembrolizumab, and nominally significant worsening was reported with docetaxel. Significant prolongation in true time to deterioration for the QLQ-LC13 composite endpoint emerged for pembrolizumab 10 mg/kg compared to docetaxel (nominal two-sided p = 0.03), but not for the 2-mg/kg dose.Conclusions
These findings suggest that HRQoL and symptoms are maintained or improved to a greater degree with pembrolizumab than with docetaxel in this NSCLC patient population. 相似文献The metabolism of the pyrethroids deltamethrin (DLM), cis-permethrin (CPM) and trans-permethrin (TPM) was studied in human expressed cytochrome P450 (CYP) and carboxylesterase (CES) enzymes.
DLM, CPM and TPM were metabolised by human CYP2B6 and CYP2C19, with the highest apparent intrinsic clearance (CLint) values for pyrethroid metabolism being observed with CYP2C19. Other CYP enzymes contributing to the metabolism of one or more of the three pyrethroids were CYP1A2, CYP2C8, CYP2C9*1, CYP2D6*1, CYP3A4 and CYP3A5. None of the pyrethroids were metabolised by CYP2A6, CYP2E1, CYP3A7 or CYP4A11.
DLM, CPM and TPM were metabolised by both human CES1 and CES2 enzymes.
Apparent CLint values for pyrethroid metabolism by CYP and CES enzymes were scaled to per gram of adult human liver using abundance values for microsomal CYP enzymes and for CES enzymes in liver microsomes and cytosol. TPM had the highest and CPM the lowest apparent CLint values for total metabolism (CYP and CES enzymes) per gram of adult human liver.
Due to their higher abundance, all three pyrethroids were extensively metabolised by CES enzymes in adult human liver, with CYP enzymes only accounting for 2%, 10% and 1% of total metabolism for DLM, CPM and TPM, respectively.