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   45721篇
  免费   4013篇
  国内免费   1393篇
耳鼻咽喉   358篇
儿科学   892篇
妇产科学   785篇
基础医学   5876篇
口腔科学   725篇
临床医学   4760篇
内科学   9810篇
皮肤病学   686篇
神经病学   2159篇
特种医学   841篇
外国民族医学   2篇
外科学   4634篇
综合类   4689篇
现状与发展   2篇
一般理论   48篇
预防医学   5116篇
眼科学   652篇
药学   3747篇
  29篇
中国医学   1277篇
肿瘤学   4039篇
  2024年   163篇
  2023年   2962篇
  2022年   6959篇
  2021年   8864篇
  2020年   6055篇
  2019年   1893篇
  2018年   1867篇
  2017年   1283篇
  2016年   1080篇
  2015年   1429篇
  2014年   2022篇
  2013年   1776篇
  2012年   1446篇
  2011年   1661篇
  2010年   1311篇
  2009年   1109篇
  2008年   1082篇
  2007年   1111篇
  2006年   915篇
  2005年   759篇
  2004年   713篇
  2003年   683篇
  2002年   423篇
  2001年   347篇
  2000年   317篇
  1999年   295篇
  1998年   395篇
  1997年   299篇
  1996年   240篇
  1995年   175篇
  1994年   145篇
  1993年   122篇
  1992年   110篇
  1991年   98篇
  1990年   69篇
  1989年   68篇
  1988年   70篇
  1987年   43篇
  1986年   43篇
  1985年   108篇
  1984年   102篇
  1983年   67篇
  1982年   79篇
  1981年   71篇
  1980年   70篇
  1979年   65篇
  1978年   36篇
  1977年   36篇
  1975年   21篇
  1973年   27篇
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
71.
《Drug discovery today》2022,27(6):1733-1742
Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action.  相似文献   
72.
The first COVID-19 vaccination was given in December 2020 and there is an effort to vaccinate the international population on a massive scale. Common side effects from the vaccine include headache and tiredness. Regional lymphadenopathy has been described in relation to other vaccines. We describe two cases of supraclavicular reactive lymphadenopathy presenting in patients who had the COVID vaccination in the ipsilateral arm. Awareness of this diagnosis is important for patients presenting to the neck lump clinic.  相似文献   
73.
There have been several clinical manifestations associated with SARS-CoV-2 infection since 2019, including dermatological signs and symptoms. In this article, the authors report a case of a previously healthy patient with COVID-19 who was mistakenly diagnosed with dengue fever due to a skin rash. By the time the patient's investigation was initiated, Joinville (Santa Catarina, Brazil) had approximately 5,000 confirmed cases of dengue fever and 1,700 cases of COVID-19 in 2020. Thus, the authors emphasize that in endemic regions such as Brazil, the two diseases must be considered until proven otherwise. Finally, the authors warn of the possibility of co-infection with these two viruses in regions that are facing both epidemics at the same time.  相似文献   
74.
Matrix metalloproteinase-11 (MMP11) is an enzyme with proteolytic activity against matrix and nonmatrix proteins. Although most MMPs are secreted as inactive proenzymes and are later activated extracellularly, MMP11 is activated intracellularly by furin within the constitutive secretory pathway. It is a key factor in physiological tissue remodeling and its alteration may play an important role in the progression of epithelial malignancies and other diseases. TCGA colon and colorectal adenocarcinoma data showed that upregulation of MMP11 expression correlates with tumorigenesis and malignancy. Here, we provide evidence that a germline variant in the MMP11 gene (NM_005940: c.232C>T; p.(Pro78Ser)), identified by whole exome sequencing, can increase the tumorigenic properties of colorectal cancer (CRC) cells. P78S is located in the prodomain region, which is responsible for blocking MMP11's protease activity. This variant was detected in the proband and all the cancer-affected family members analyzed, while it was not detected in healthy relatives. In silico analyses predict that P78S could have an impact on the activation of the enzyme. Furthermore, our in vitro analyses show that the expression of P78S in HCT116 cells increases tumor cell invasion and proliferation. In summary, our results show that this variant could modify the structure of the MMP11 prodomain, producing a premature or uncontrolled activation of the enzyme that may contribute to an early CRC onset in these patients. The study of this gene in other CRC cases will provide further information about its role in CRC development, which might improve patient treatment in the future.  相似文献   
75.
Coronavirus disease 2019 (COVID-19) is associated with a high risk of mortality and complications in patients with diabetes mellitus. Achieving good glycemic control is very important in diabetic patients to reduce complications and mortality due to COVID-19. Recent studies have shown the mortality benefit and anti-inflammatory effects of Dipeptidyl-peptidase-4 inhibitors (DPP-4i) in diabetic patients with COVID-19. DPP-4i may have a beneficial role in halting the severity of infection primarily by three routes, namely viral entry inhibition, anti-inflammatory and anti-fibrotic effects and glycemic control. This has raised the pro-mising hypothesis that DPP-4i might be an optimal strategy for treating COVID-19 in patients with diabetes. This review aims to summarise the possible therapeutic non-glycemic effects of DPP-4i in diabetic patients diagnosed with COVID-19 in the light of available evidence.  相似文献   
76.
Objectives:To reassess the long-term camouflage effects of resin infiltration (Icon, DMG, Hamburg, Germany) of white spot lesions (WSL) and sound adjacent enamel (SAE) achieved in a previous trial. The null hypothesis was tested that there were no significantly different CIE-L*a*b*-ΔE-values between WSL and SAE areas of assessment after at least 24 months (T24) compared to those at baseline (T0).Materials and Methods:Of twenty subjects who received previous resin infiltration treatment of nteeth = 111 nonrestored, noncavitated postorthodontic WSL after multibracket treatment during a randomized controlled trial and were contacted 20 months after baseline, eight subjects (trial teeth nteeth = 40; m/f ratio 1/7; age range (mean; SD) 12–17 [15.25; 2.12] years); response rate: 40%) were available for follow-up after at least 24 months (T24). CIE-L*a*b* differences between summarized color and lightness values (ΔEWSL/SAE) of WSL and SAE were assessed using a spectrophotometer and compared to baseline data assessed prior to infiltration (T0), and those after 6 (T6), and 12 (T12) months using paired t tests at a significance level of α = 5%.Results:T24 assessments were performed after a mean 33.86 (SD: 8.64; Min: 24; Max: 45) months following T0. Mean (SD) ΔEWSL/SAE units of available teeth were 8.76 (5.33) at baseline; 5.5 (2.75) at T6; 5.2 (2.41) at T12; and 5.57 (2.6) at T24. Comparisons of T6, T12, and T24 with T0 yielded highly significant differences, whereas T6–T24 and T12–T24 differences were found to be not significant.Conclusions:Assimilation of infiltrated WSL to the color of adjacent enamel by resin infiltration is considered to be suitable for the long-term improvement in the esthetic appearance of postorthodontic WSL.  相似文献   
77.
《Pancreatology》2022,22(5):665-670
Background and objectivesHyperlipasemia is highly prevalent among coronavirus disease 2019 (COVID-19) patients. The aim of this study was to assess the effect of lipase activity, measured at the time of admission, on the clinical course and mortality in COVID-19 patients.MethodsThe population of this study comprised 12,139 patients who were hospitalized due to COVID-19 between June 2020 and June 2021 in a pandemic hospital. Of these, 8819 patients were excluded from the study due to missing data, four patients were excluded due to a diagnosis of acute pancreatitis (according to the revised Atlanta criteria), and 72 patients were excluded due to alcohol use or having a history of chronic pancreatitis. The final study sample consisted of the remaining 3244 COVID-19 patients. Laboratory results, intensive care unit (ICU) follow-up periods, the need for mechanical ventilation, and mortality rates were compared between the normal lipase activity and high lipase activity groups.ResultsThere were 968 (29.8%) patients with high lipase activity at the time of admission. The rate of ICU admission was 36.1% vs. 9.9% (p < 0.001), mechanical ventilation requirement rates were 33.7% vs. 8.3% (p < 0.001), and mortality rates were as 24.6% vs. 6.4% (p < 0.001) in the high lipase activity group compared to the normal lipase activity group. Multivariate regression analysis revealed that high lipase activity was an independent factor in predicting mortality in hospitalized COVID-19 patients (odds ratio [OR]: 3.191, p < 0.001).ConclusionElevated lipase activity without acute pancreatitis at the time of admission in COVID-19 patients was determined as an independent predictor of poor prognosis.  相似文献   
78.
肺癌是世界上发病率最高的癌症之一,且尚无二线进展后的标准治疗方案,而肿瘤血管生成目前已被确定为恶性肿瘤的重要治疗靶点,小分子多靶点血管激酶抑制剂可通过抑制血管生成相关信号通路,抑制肿瘤血管的生成。目前已开展多项小分子抗血管生成药物治疗非小细胞肺癌的临床试验,且已有部分血管内皮生长因子受体酪氨酸激酶抑制剂(vascular endothelial growth factor receptor-tyrosine kinase inhibitors, VEGFR-TKIs)获批治疗晚期非小细胞肺癌,本文基于国内外多项小分子抗血管生成药物治疗非小细胞肺癌的发展现状,归纳了多个VEGFR-TKIs及成纤维细胞生长因子受体(fibroblast growth factor receptor, FGFR)-TKI单药或联合[包括分别与化疗、表皮生长因子受体(epidermal growth factor receptor, EGFR)-TKIs、免疫治疗、放疗等联合)]治疗非小细胞肺癌的疗效与安全性研究,同时探讨了VEGFR-TKIs可能存在的耐药机制及疗效预测指标等,并对未来抗血管治疗非小细胞肺癌的发展趋势以及存在的潜在问题进行展望,同时为肺癌后续的精准治疗及个体化治疗提供新的思路。  相似文献   
79.
Cadmium is a toxic metal that can damage the brain and other organs. This study aimed to explore the protective effects of Potentilla anserine L. polysaccharide (PAP) against CdCl2-induced neurotoxicity in N2a and SH-SY5Y cells and in the cerebral cortex of BALB/c mice. In addition, we aimed to identify the potential mechanisms underlying these protective effects. Relative to CdCl2 treatment alone, pretreatment with PAP prevented the reduction in cell viability evoked by CdCl2, decreased rates of apoptosis, promoted calcium homeostasis, decreased ROS accumulation, increased mitochondrial membrane potential, inhibited cytochrome C and AIF release, and prevented the cleavage of caspase-3 and PARP. In addition, PAP significantly decreased the CdCl2-induced phosphorylation of CaMKII, Akt, and mTOR. In conclusion, PAP represents a potential therapeutic agent for the treatment of Cd-induced neurotoxicity, functioning in part via attenuating the activation of the mitochondrial apoptosis pathway and the Ca2+-CaMKII-dependent Akt/mTOR pathway.  相似文献   
80.
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