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1.
Hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer is defined by the presence of the estrogen receptor and/or the progesterone receptor and the absence of HER2 gene amplification. HR-positive/HER2-negative breast cancer accounts for 65%–70% of all breast cancers, and incidence increases with increasing age. Treatment varies by stage, and endocrine therapy is the mainstay of treatment in both early stage and late-stage disease. Combinations with cyclin-dependent kinase 4/6 inhibitors have reduced distant recurrence in the early stage setting and improved overall survival in the metastatic setting. Chemotherapy is used based on stage and tumor biology in the early stage setting and after endocrine resistance for advanced disease. New therapies, including novel endocrine agents and antibody-drug conjugates, are now changing the treatment landscape. With the availability of new treatment options, it is important to define the optimal sequence of treatment to maximize clinical benefit while minimizing toxicity. In this review, the authors first discuss the pathologic and molecular features of HR-positive/HER2-negative breast cancer and mechanisms of endocrine resistance. Then, they discuss current and emerging therapies for both early stage and metastatic HR-positive/HER2-negative breast cancer, including treatment algorithms based on current data.  相似文献   
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In Australia's HPV-based cervical screening program, we previously showed that risk of histological high-grade abnormality at 1 year post screening decreased with age in women with oncogenic HPV. In this study, we followed 878 HPV16/18 positive women aged 55 years and over for up to 3 years post screening test, to determine the proportion with histological high-grade abnormality (HGA, incorporating high-grade squamous intraepithelial abnormality (HSIL), adenocarcinoma in situ (AIS), squamous cell carcinoma (SCC) and adenocarcinoma) and to correlate risk of HGA with liquid-based cytology result and with prior screening history. HGA was detected in 7.8% at 1 year and 10.0% at 3 years, with no significant difference (P = .136), despite the number of women with follow-up information significantly increasing from 82.9% to 91.0% (P < .0001). The proportion of HPV16/18 positive women with HGA at 3 years was highest in those with an HSIL cytology result (79.0%) and lowest in those with negative cytology (6.2%). Women with an adequate screening history had fewer HGA than such women with inadequate prior screening (6.6% vs 16.0%, P = .001) or with a history of an abnormality (6.6% vs 14.4%, P = .001). HPV16/18 infection in women over 55 years may have a different natural history from that in younger women, in whom HGA are more common after HPV16/18 detection. In HPV-based cervical screening programs, management algorithms for screen-detected abnormalities based on risk stratification should include factors such as age, screening history and index cytology result, so that women receive appropriate investigation and follow-up.  相似文献   
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Human papillomavirus (HPV) vaccine effectiveness may differ between settings. Here we present the first real-world effectiveness study of HPV vaccination on high-grade cervical lesions from Norway, among women who received HPV vaccine outside the routine program. We performed an observational study of all Norwegian women born 1975 to 1996 and retrieved individual data from nationwide registries on HPV vaccination status and incidence of histologically verified high-grade cervical neoplasia during 2006 to 2016. We estimated the incidence rate ratio (IRR) and 95% confidence intervals (CI) for vaccination vs no vaccination by Poisson regression stratified by age at vaccination <20 years and ≥20 years. The cohort consisted of 832 732 women, of which 46 381 (5.6%) received at least one dose of HPV vaccine by the end of 2016. The incidence rate of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) increased with age regardless of vaccination status and was highest at age 25 to 29, at 637/100 000 among unvaccinated women, 487/100 000 among women vaccinated before age 20 and 831/100 000 among women vaccinated at age 20 or older. The adjusted IRR of CIN2+ between vaccinated and unvaccinated women was 0.62 (95% CI: 0.46-0.84) for women vaccinated below age 20, and 1.22 (95% CI: 1.03-1.43) for women vaccinated at age 20 or older. These findings indicate that HPV vaccination among women too old to be eligible for routine HPV vaccination is effective among women who are vaccinated below age 20 but may not have the desired impact among women who are vaccinated at age 20 or older.  相似文献   
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Sexual minority men are at increased risk for anal squamous cell carcinoma. Our objective was to compare screening engagement among individuals randomized to self-collect an anal canal specimen at home or to attend a clinic appointment. Specimen adequacy was then assessed for human papillomavirus (HPV) DNA genotyping. A randomized trial recruited cisgendered sexual minority men and transgender people in the community and assigned them to use a home-based self-collection swabbing kit or attend a clinic-based swabbing. Swabs were sent for HPV genotyping. The proportions of participants completing screening in each study arm and the adequacy of their specimens for HPV genotyping were assessed. Relative risks were estimated for factors associated with screening. A total of 240 individuals were randomized. Age (median, 46 years) and HIV status (27.1% living with HIV) did not differ by study arm. A total of 89.2% and 74.2% of home-arm and clinic-arm individuals returned the swab, respectively (P = .003), difference between groups, 15.0% (95% CI 5.4%-24.6%). Among black individuals, 96.2% and 63.2% in the home and clinic arms screened (P = .006). Among individuals with HIV, 89.5% and 51.9% in the home and clinic arms screened (P < .001). Self-collected swabs and clinician-collected swabs were comparable in adequacy for HPV genotyping (96.3% and 93.3%, respectively). People at highest risk for anal cancer may be more likely to screen if they are able to self-collect swabs at home rather than attend a clinic.  相似文献   
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目的观察蜚蠊提取液联合干扰素对宫颈持续性高危型人乳头瘤病毒(high-risk human papillomavirus, HR-HPV)感染的治疗效果,并比较治疗前后阴道微生态及宫颈局部细胞免疫功能变化。方法按病例纳入和排除标准纳入宫颈持续性HR-HPV感染患者80例随机分为2组,每组40例,对照组使用干扰素阴道纳入治疗,研究组在对照组的基础上加用蜚蠊提取液进行阴道冲洗,两组均治疗3个疗程。在治疗前后分别进行宫颈HR-HPV检测、阴道微生态评价及宫颈细胞免疫功能检测。结果治疗后研究组宫颈持续性HR-HPV感染转为阴性24例(61.54%),对照组转为阴性13例(33.33%),研究组治疗宫颈持续性HR-HPV感染的效果明显优于对照组(χ2=6.221,P=0.013);研究组治疗后阴道微生态失衡(χ2=6.642,P=0.010)、乳杆菌分级异常(Ⅱb或Ⅲ级,χ2=6.271,P=0.012)、革兰阴性短杆菌(χ2=7.508,P=0.006)、革兰阳性球菌(χ2=8.419,P=0.004)、pH值异常(χ2=4.198,P=0.040)、H2O2阳性(χ2=5.769,P=0.016)及AV检出(χ2=4.255,P=0.039)等指标较治疗前得到明显改善(P<0.05);对照组治疗后仅在pH值异常改善方面与治疗前差异有统计学意义(χ2=7.429,P=0.006);两组间治疗后比较,研究组对阴道微生态失衡的治疗效果较对照组更明显,具有显著性差异(χ2=4.446,P=0.035);治疗后研究组宫颈细胞免疫功能改善比对照组更明显,CD4(t=-4.741,P<0.001)、CD8(t=-4.725,P<0.001)、CD4/CD8(Z=-5.022,P<0.001)、TNF-α(t=-4.912,P<0.001)、IL-4(t=-2.162,P=0.034)差异均具有统计学意义(P<0.05)。结论蜚蠊提取液清利湿热、活血解毒等功效,与干扰素合用可显著提高宫颈持续性HR-HPV感染的治疗效果,其作用可能与通过纠正阴道微生态失衡及改善宫颈局部细胞免疫功能相关。  相似文献   
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徐博 《当代医学》2022,28(4):44-46
目的探讨左西孟旦、重组人脑利钠肽联合米力农治疗顽固性心力衰竭(RHF)患者对其血清内皮素-1(ET-1)、醛固酮(ALD)水平的影响。方法选取2018年8月至2020年8月于本院进行治疗的80例RHF患者作为研究对象,采用简单随机分组法分为A组和B组,各40例。A组采用左西孟旦(LEV)联合米力农治疗,B组采用重组人脑利钠肽(rh-BNP)联合米力农治疗,比较两组临床疗效、不良反应发生情况、ET-1、ALD、左心室射血分数(LVEF)、N末端B型利尿钠肽原(NT-proBNP)水平以及6 min步行试验距离(6MWT)。结果 A组治疗总有效率为97.50%,高于B组的85.00%(P<0.05)。治疗7 d后,两组LVEF和6MWT距离均大于治疗前(P<0.05),NT-proBNP水平均低于治疗前,且A组LVEF和6MWT距离大于B组,NT-proBNP水平低于B组(P<0.05)。治疗7 d后,两组ET-1、ALD水平均低于治疗前,且A组低于B组(P<0.05)。A组不良反应发生率为12.50%,低于B组的32.50%(P<0.05)。结论 LEV、rh-BNP联合米力农治疗RHF患者均可取得显著疗效,但LEV联合米力农改善患者心功能、降低ET-1和ALD水平的效果更显著,且不良反应较少。  相似文献   
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目的探讨在牙龈卟啉单胞菌脂多糖(P.g-LPS)刺激的炎症环境下,人牙周膜成纤维细胞(hPDLFs)中溶质载体家族7成员11(SLC7A11)和谷胱甘肽过氧化物酶4(GPX4)表达的变化,阐明P.g-LPS诱导牙周炎的可能机制。  相似文献   
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目的观察重组人生长激素对局灶性脑缺血再灌注小鼠运动功能的影响,探讨其可能的作用机制。  相似文献   
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