全文获取类型
收费全文 | 19726篇 |
免费 | 1126篇 |
国内免费 | 757篇 |
专业分类
耳鼻咽喉 | 81篇 |
儿科学 | 199篇 |
妇产科学 | 206篇 |
基础医学 | 3075篇 |
口腔科学 | 277篇 |
临床医学 | 2072篇 |
内科学 | 2515篇 |
皮肤病学 | 318篇 |
神经病学 | 649篇 |
特种医学 | 355篇 |
外国民族医学 | 4篇 |
外科学 | 647篇 |
综合类 | 2800篇 |
现状与发展 | 1篇 |
预防医学 | 2343篇 |
眼科学 | 168篇 |
药学 | 4005篇 |
3篇 | |
中国医学 | 646篇 |
肿瘤学 | 1245篇 |
出版年
2023年 | 149篇 |
2022年 | 267篇 |
2021年 | 408篇 |
2020年 | 483篇 |
2019年 | 459篇 |
2018年 | 420篇 |
2017年 | 480篇 |
2016年 | 551篇 |
2015年 | 533篇 |
2014年 | 1119篇 |
2013年 | 1369篇 |
2012年 | 1247篇 |
2011年 | 1453篇 |
2010年 | 1032篇 |
2009年 | 981篇 |
2008年 | 989篇 |
2007年 | 1034篇 |
2006年 | 900篇 |
2005年 | 920篇 |
2004年 | 795篇 |
2003年 | 692篇 |
2002年 | 617篇 |
2001年 | 490篇 |
2000年 | 430篇 |
1999年 | 345篇 |
1998年 | 292篇 |
1997年 | 270篇 |
1996年 | 230篇 |
1995年 | 260篇 |
1994年 | 234篇 |
1993年 | 181篇 |
1992年 | 189篇 |
1991年 | 190篇 |
1990年 | 182篇 |
1989年 | 158篇 |
1988年 | 143篇 |
1987年 | 123篇 |
1986年 | 115篇 |
1985年 | 216篇 |
1984年 | 150篇 |
1983年 | 132篇 |
1982年 | 110篇 |
1981年 | 64篇 |
1980年 | 50篇 |
1979年 | 45篇 |
1978年 | 23篇 |
1977年 | 24篇 |
1975年 | 9篇 |
1974年 | 19篇 |
1972年 | 9篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
1.
2.
《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
3.
《Vaccine》2022,40(24):3380-3388
BackgroundWe evaluated the safety and immunogenicity of NVX-CoV2373, a recombinant SARS-CoV-2 nanoparticle vaccine, in healthy Japanese participants.MethodsThis phase 1/2, randomized, observer-blind, placebo-controlled trial conducted in Japan (two sites), enrolled healthy Japanese adults aged ≥ 20 years with no history/risk of SARS-CoV-2 infection and no prior exposure to other approved/investigational SARS-CoV-2 vaccines or treatments. Participants were stratified by age (< 65 or ≥ 65 years) and randomized to receive two doses of either NVX-CoV2373 (5 μg SARS-CoV-2 rS; 50 μg Matrix-M1) or placebo, 21 days apart. Primary outcomes were safety and immunogenicity assessed by serum IgG antibody levels against SARS-CoV-2 rS protein on day 36. Herein, we report the primary data analysis at 4 weeks after the second dose, ahead of 12-month follow-up completion (data cut-off: 8 May 2021).ResultsBetween 12 February 2021 and 17 March 2021, 326 subjects were screened, and 200 participants enrolled and randomized: NVX-CoV2373, n = 150; placebo, n = 50. Solicited adverse events (AEs) through 7 days after each injection occurred in 121/150 (80.7%) and 11/50 (22.0%) participants in the NVX-CoV2373 and placebo arms, respectively. In the NVX-CoV2373 arm, tenderness and injection site pain were the most frequently reported solicited AEs after each vaccination, irrespective of age. Robust immune responses occurred with NVX-CoV2373 (n = 150) by day 36: IgG geometric mean fold rise (95% confidence interval) 259 (219, 306); seroconversion rate 100% (97.6, 100). No such response occurred with placebo (n = 49).ConclusionTwo doses of NVX-CoV2373 given with a 21-day interval demonstrated acceptable safety and induced robust anti-SARS-CoV-2 immune responses in healthy Japanese adults. Funding: Takeda Pharmaceutical Company Limited and Japan Agency for Medical Research and Development (AMED). ClinicalTrials.gov identifier: NCT04712110. 相似文献
4.
《Vaccine》2022,40(6):934-944
Respiratory Syncytial Virus (RSV) remains a leading cause of severe respiratory disease for which no licensed vaccine is available. We have previously described the derivation of an RSV Fusion protein (F) stabilized in its prefusion conformation (preF) as vaccine immunogen and demonstrated superior immunogenicity in naive mice of preF versus wild type RSV F protein, both as protein and when expressed from an Ad26 vaccine vector. Here we address the question if there are qualitative differences between the two vaccine platforms for induction of protective immunity. In naïve mice, both Ad26.RSV.preF and preF protein induced humoral responses, whereas cellular responses were only elicited by Ad26.RSV.preF. In RSV pre-exposed mice, a single dose of either vaccine induced cellular responses and strong humoral responses. Ad26-induced RSV-specific cellular immune responses were detected systemically and locally in the lungs. Both vaccines showed protective efficacy in the cotton rat model, but Ad26.RSV.preF conferred protection at lower virus neutralizing titers in comparison to RSV preF protein. Factors that may contribute to the protective capacity of Ad26.RSV.preF elicited immunity are the induced IgG2a antibodies that are able to engage Fcγ receptors mediating Antibody Dependent Cellular Cytotoxicity (ADCC), and the induction of systemic and lung resident RSV specific CD8 + T cells. These data demonstrate qualitative improvement of immune responses elicited by an adenoviral vector based vaccine encoding the RSV preF antigen compared to the subunit vaccine in small animal models which may inform RSV vaccine development. 相似文献
5.
We aimed to study the rate of isoniazid (INH) resistance in Extrapulmonary Tuberculosis samples from a private care setting.A Line probe assay was performed on 74 culture isolates of Mycobacterium tuberculosis or directly on extrapulmonary samples received in our laboratory from 2018 to 2021.The INH mono-resistance among these extrapulmonary samples was 6.7%. (5 among 74) (95% CI: 1.04%–12.48%) Resistance to rifampicin was not detected.Increasing the availability and leveraging public private partnerships in hospitals for universal testing for INH resistance may increase detection of INH monoresistance in EP-TB and improve the strategy for TB elimination. 相似文献
6.
《Saudi Pharmaceutical Journal》2022,30(11):1665-1671
5-fluorouracil (5FU) is widely used to treat colorectal cancer (CC) and its main mechanisms of anticancer action are through generation of ROS which often result in inflammation. Here, we test the effect of Lycopene against 5FU in Caco2 cell line. Caco2 cells were exposed to 3 µg/ml of 5FU alone or with 60, 90, 120 µg/ml of lycopene. This was followed by assessment of cytotoxicity, oxidative stress, and gene expression of inflammatory genes. Our findings showed that Lycopene and 5FU co-exposure induced dose-dependent cytotoxic effect without compromising the membrane integrity based on the LDH assay. Lycopene also significantly enhanced 5FU-induced SOD activity and GSH level compared to control for all mixture concentrations (p < 0.01). Lycopene alone and combination with 5FU-induced expression of IL-1β, TNF-α, and IL-6. Furthermore, IFN-γ expression was significantly enhanced by only mixture of lycopene (90 µg/ml) and 5FU (p < 0.05). In conclusion, Lycopene supplementation with 5FU therapy resulted in improvement in antioxidant parameters such as catalase and GSH levels giving the cell capacity to cope with 5FU-mediated oxidative stress. Lycopene also enhanced IFN-γ expression in the presence of 5FU, which may activate antitumor effects further enhancing the cancer killing effect of 5FU. 相似文献
7.
目的 调查石河子地区近十年结肠镜下成人结直肠癌(colorectal cancer,CRC)、结直肠腺瘤和进展期腺瘤检出率的变化趋势。方法 2010年1月1日—2019年12月31日期间,就诊于石河子大学医学院第一附属医院完成结肠镜检查的病例纳入调查,通过查阅电子病历系统收集病历资料,具体信息包括患者年龄、性别及结直肠腺瘤或CRC的部位、数量、大小和病理类型等。主要观察结直肠腺瘤、结直肠进展期腺瘤和CRC的检出率,包括10年总体检出率以及前五年(2010—2014年)总体检出率和后五年(2015—2019年)总体检出率。结果 共纳入50 645例,经排除标准排除14 931例,最终共35 714例纳入数据分析。结直肠腺瘤、结直肠进展期腺瘤和CRC的10年总体检出率分别为17.65%(6 302/35 714)、4.45%(1 589/35 714)和3.71%(1 324/35 714)。结直肠腺瘤后五年总体检出率[20.33%(4 565/22 457)]高于前五年[13.10%(1 737/13 257)];结直肠进展期腺瘤后五年总体检出率[4.69%(1 053/22 457)]高于前五年[4.04%(536/13 257)];CRC后五年总体检出率[3.30%(741/22 457)]低于前五年[4.40%(583/13 257)]。结论 石河子地区2015—2019年结直肠腺瘤检出率较2010—2014年有较大幅度升高,结直肠进展期腺瘤检出率较2010—2014年有小幅升高,而CRC检出率较2010—2014年有小幅下降,由此推测结肠镜检查发现并切除结直肠腺瘤对降低CRC发病率可能具有重要作用。 相似文献
8.
《Journal of microbiology, immunology, and infection》2022,55(2):328-331
The ichroma? IGRA-TB (Boditech Med Inc., Chuncheon, Republic of Korea) is an automated fluorescent immunoassay-based point-of-care interferon-gamma release assay for detecting latent tuberculosis infection. We evaluated this assay with 408 health care workers, and demonstrated its acceptable performances comparing to QuantiFERON-TB Gold-Plus (QFT-Plus; Qiagen, Germantown, MD). 相似文献
9.
10.
《Clinical lung cancer》2020,21(1):56-65.e8
BackgroundThe introduction of liquid biopsy using PCR-based assays into routine practice has had a strong impact on the treatment of EGFR-mutated lung adenocarcinoma and is now commonly used for routine testing of EGFR mutations in certain clinical settings. To assess whether the claimed benefits of PCR-based assays hold true in daily practice at a multicenter clinical institution, we assessed how treatment decisions are affected by PCR-based assays for the analysis of EGFR mutations from plasma samples in a centralized laboratory (LPCE, Nice, France).Patients and MethodsA total of 345 samples were analyzed using the US Food and Drug Administration–approved Cobas EGFR Mutation Test v2 and 103 using the Therascreen EGFR Plasma RGQ PCR Kit over 3 years (395 samples from 324 patients). Eleven plasma samples were validated independently using Cobas at 3 institutions, and 130 samples were analyzed using Stilla digital PCR. Clinical data were collected for 175 (54%) of 324 patients.ResultsCobas was superior to the Therascreen assay and demonstrated 100% reproducibility. Digital PCR showed only 48%, 83%, and 58% concordance with Cobas for exon 19 deletions, L858R mutations, and T790M mutations, respectively. Liquid biopsies helped inform and change treatment when resistance occurred and enabled the detection of EGFR mutations in patients when biopsy tissue results were unavailable.ConclusionPCR-based assays are a fast and convenient test, allowing the detection of primary and secondary EGFR mutations from plasma. Cobas proved to be a reliable test, whereas digital PCR produced too many inconclusive results to be currently recommended as a principal testing device. 相似文献