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摘要:目的 通过应用全基因组测序(whole genome sequencing, WGS)技术分析某三级医疗机构耐碳青霉烯类抗生素鲍曼不 动杆菌(carbapenem-resistant Acinetobacter baumannii, CRAB)的耐药基因、毒力因子及同源性。方法 收集该院2020年1月至3月 重症监护病房(Intensive care unit, ICU)、神经外科分离的11株医院感染CRAB菌株,通过二代测序平台进行全基因组测序, 应用 基因组流行病学中心(Center for genomic epidemiology, CGE)ResFinder 4. 0软件分析其耐药基因型,并应用MORPHEUS在线制作 热图,应用毒力因子数据库(virulence factors of pathogenic bacteria, VFDB)VFanalyzer软件筛选毒力因子,应用MLST软件检测菌 株的ST型,应用Kaptive软件检测荚膜型,应用CSI Phylogeny 1. 4软件及FigTree v1. 4. 4软件构建最大似然树(maximum likelihood tree, MLT)以分析其同源性。结果 11株CRAB对亚胺培南、美罗培南、头孢菌素、环丙沙星均呈现耐药,而对阿米卡星、左氧 氟沙星耐药的菌株株数较少。11株CRAB共检测出18种耐药基因,11株同时携带碳青霉烯酶耐药基因blaOXA-23和blaOXA-66,β-内酰 胺酶耐药基因以blaTEM-1D和blaADC-25为主,大部分菌株携带多种外排泵相关耐药基因及抗菌药物修饰酶耐药基因。11株CRAB均携 带多种毒力因子,包括外膜孔蛋白、脂多糖、生物膜、外排泵、磷脂酶和效应蛋白等,如OmpA、Lps、Csu、Pga、Ade、Plc、 Bas、Bau、Ent、Hem、Aba、Bfm、Pbp和Kat等。11株CRAB均为ST2-K22型,同源性分析结果显示C组内同源性关系相近,存 在院内传播的可能。结论 该院CRAB的耐药性、毒力特征复杂多样,同源性分析显示该院存在1种优势克隆株,该克隆株有医 院内传播的风险。  相似文献   
3.
目的用几种高度精细灵敏的方法检测氧糖剥夺再复氧(OGD/R)后神经元自噬流不同阶段的变化。方法原代皮质神经元细胞经过OGD/R后将实验分为OGD/R组及OGD/R+bafilomycin A1 (BafA1)组,用RFP-GFP串联荧光标记LC3基因转染检测自噬小体和溶酶体的融合情况,透射电子显微镜(TEM)观察自噬的超微结构,SQSTM1/p62结合LC3蛋白翻转实验检测p62与LC3蛋白的定量,p62免疫染色观测其分布与含量。结果荧光显微镜下OGD/R组自噬溶酶体与自噬小体比值明显增高;TEM可观测到不同阶段的自噬结构变化;可溶性p62的比值结合LC3Ⅱ/Ⅰ的比值共同反映了自噬流的活化;p62荧光染色后在BafA1组中分布居多。结论每种方法各有其优点,不同方法和指标能够精准地反映神经元OGD/R后自噬流在不同阶段的具体变化,掌握并应用好这些方法能有效从自噬角度探索中枢神经系统疾病。  相似文献   
4.
Numerous studies showed that postural balance improves through light touch on a stable surface highlighting the importance of haptic information, seemingly downplaying the mechanical contributions of the support. The present study examined the mechanical effects of canes for assisting balance in healthy individuals challenged by standing on a beam. Sixteen participants supported themselves with two canes, one in each hand, and applied minimal, preferred, or maximum force onto the canes. They positioned the canes in the frontal plane or in a tripod configuration. Statistical analysis used a linear mixed model to evaluate the effects on the center of pressure and the center of mass. The canes significantly reduced the variability of the center of pressure and the center of mass to the same level as when standing on the ground. Increasing the exerted force beyond the preferred level yielded no further benefits, although in the preferred force condition, participants exploited the altered mechanics by resting their arms on the canes. The tripod configuration allowed for larger variability of the center of pressure in the task-irrelevant anterior–posterior dimension. High forces had a destabilizing effect on the canes: the displacement of the hand on the cane handle increased with the force. Given this static instability, these results show that using canes can provide not only mechanical benefits but also challenges. From a control perspective, effort can be reduced by resting the arms on the canes and by channeling noise in the task-irrelevant dimensions. However, larger forces exerted onto the canes can also have destabilizing effects and the instability of the canes needs to be counteracted, possibly by arm and shoulder stiffness. Insights into the variety of mechanical effects is important for the design of canes and the instructions of how to use them.  相似文献   
5.
目的探究甲磺酸去铁胺对精索静脉曲张睾丸支持细胞氧化应激模型的保护作用。方法细胞实验选择小鼠睾丸支持细胞TM-4,设置对照组(A组)、甲磺酸去铁胺+对照组(B组)、氯化钴组(C组)、甲磺酸去铁胺+氯化钴组(D组)。C组和D组加入400μmol/L氯化钴,随后培养细胞24 h构建精索静脉曲张氧化应激模型。B组和D组加入800μmol/L甲磺酸去铁胺。采用细胞计数试剂盒(CCK-8)和流式测定细胞存活和凋亡水平;采用酶联免疫吸附试验(ELISA)法测定细胞内活性氧(ROS)、十二烷硫酸钠(SDS)、丙二醛(malondialdehyde,MDA)、谷胱甘肽(GSH)水平;采用蛋白质印迹法(Western blot)检测谷胱甘肽过氧化物酶-4(GPX4)的蛋白表达水平,组间比较采用t检验。结果CCK-8实验结果显示C组和D组细胞存活率低于A组[(45.75±12.08)%、(86.53±2.57)%比(100.00±0.00)%,t=11.000、12.810,P值均<0.05],差异有统计学意义,且D组细胞存活率高于C组[(86.53±2.57)%比(45.75±12.08)%,t=8.087,P<0.01],差异有统计学意义。流式实验结果显示D组凋亡细胞比例低于C组[(8.63±0.11)%比(34.19±0.35)%,t=121.300,P<0.01],差异有统计学意义。ELISA结果显示D组相对ROS、MDA表达水平低于C组[(239.17±23.18)%、(40.34±1.50)nmol/(L·mg)比(378.00±24.84)%、(49.18±2.68)nmol/(L·mg),t=10.010、7.053,P值均<0.01];超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)表达水平高于C组[(7.85±0.24)U/mg、(425.60±12.21)U/mg比(4.69±0.28)U/mg、(208.96±7.00)U/mg,t=20.650、37.710,P<0.01],差异均有统计学意义。蛋白质印迹法实验结果显示氯化钴缺氧诱导了铁死亡关键蛋白GPX4表达下调,而甲磺酸去铁胺(DFO)恢复了铁死亡关键蛋白GPX4的表达。结论甲磺酸去铁胺通过抑制铁死亡对精索静脉曲张睾丸支持细胞氧化应激模型起保护作用。  相似文献   
6.
Obesogens are a subset of endocrine disruptor chemicals (EDCs) that cause obesity. The typical EDC 4-nonylphenol (4-NP) has been identified as an obesogen. However, the in vitro effects of 4-NP on adipogenesis remain unclear. In this study, 3T3-L1 preadipocytes and C3H/10T1/2 mesenchymal stem cells (MSCs) were used to investigate the influence of 4-NP on adipogenesis. The differentiation protocols for 3T3-L1 preadipocytes and C3H/10T1/2 MSCs took 8 and 12 days, respectively, beginning at Day 0. In differentiated 3T3-L1 preadipocytes, 20 μM 4-NP decreased cell viability on Days 4 and 8. Exposure to 4-NP inhibited triglyceride (TG) accumulation and adipogenic marker expression on Days 0–8, but the inhibitory effects were weaker on Days 2–8. The protein expression of pSTAT3 or STAT3 decreased on Days 0–8 and 2–8. Conversely, 4-NP promoted TG accumulation and the adipogenic marker expression in C3H/10T1/2 adipocytes. The opposing effects were attributed to physiological differences between the two cell lines. The 3T3-L1 preadipocytes are dependent on mitotic clonal expansion (MCE) to drive differentiation, while C3H/10T1/2MSCs and human preadipocytes are not. Additionally, 4-NP downregulated β-catenin expression in C3H/10T1/2 adipocytes. Accordingly, we hypothesized that 4-NP promotes adipogenesis. The role of the canonical Wnt pathway in the promotion of adipogenesis by 4-NP requires further validation. This study provides new insights into the mechanisms and appropriate risk management of 4-NP.  相似文献   
7.
Thomas Behrens  Calvin Ge  Roel Vermeulen  Benjamin Kendzia  Ann Olsson  Joachim Schüz  Hans Kromhout  Beate Pesch  Susan Peters  Lützen Portengen  Per Gustavsson  Dario Mirabelli  Pascal Guénel  Danièle Luce  Dario Consonni  Neil E. Caporaso  Maria Teresa Landi  John K. Field  Stefan Karrasch  Heinz-Erich Wichmann  Jack Siemiatycki  Marie-Elise Parent  Lorenzo Richiardi  Lorenzo Simonato  Karl-Heinz Jöckel  Wolfgang Ahrens  Hermann Pohlabeln  Guillermo Fernández-Tardón  David Zaridze  John R. McLaughlin  Paul A. Demers  Beata Świątkowska  Jolanta Lissowska  Tamás Pándics  Eleonora Fabianova  Dana Mates  Vladimir Bencko  Lenka Foretova  Vladimír Janout  Paolo Boffetta  Bas Bueno-de-Mesquita  Francesco Forastiere  Kurt Straif  Thomas Brüning 《International journal of cancer. Journal international du cancer》2023,152(4):645-660
There is limited evidence regarding the exposure-effect relationship between lung-cancer risk and hexavalent chromium (Cr(VI)) or nickel. We estimated lung-cancer risks in relation to quantitative indices of occupational exposure to Cr(VI) and nickel and their interaction with smoking habits. We pooled 14 case-control studies from Europe and Canada, including 16 901 lung-cancer cases and 20 965 control subjects. A measurement-based job-exposure-matrix estimated job-year-region specific exposure levels to Cr(VI) and nickel, which were linked to the subjects' occupational histories. Odds ratios (OR) and associated 95% confidence intervals (CI) were calculated by unconditional logistic regression, adjusting for study, age group, smoking habits and exposure to other occupational lung carcinogens. Due to their high correlation, we refrained from mutually adjusting for Cr(VI) and nickel independently. In men, ORs for the highest quartile of cumulative exposure to CR(VI) were 1.32 (95% CI 1.19-1.47) and 1.29 (95% CI 1.15-1.45) in relation to nickel. Analogous results among women were: 1.04 (95% CI 0.48-2.24) and 1.29 (95% CI 0.60-2.86), respectively. In men, excess lung-cancer risks due to occupational Cr(VI) and nickel exposure were also observed in each stratum of never, former and current smokers. Joint effects of Cr(VI) and nickel with smoking were in general greater than additive, but not different from multiplicative. In summary, relatively low cumulative levels of occupational exposure to Cr(VI) and nickel were associated with increased ORs for lung cancer, particularly in men. However, we cannot rule out a combined classical measurement and Berkson-type of error structure, which may cause differential bias of risk estimates.  相似文献   
8.
Journal of Pharmacokinetics and Pharmacodynamics - Clinical trials in patients with ulcerative colitis (UC) face the challenge of high and variable placebo response rates. The Mayo Clinical Score...  相似文献   
9.
目的 探究慢性炎性疼痛对小鼠肠道菌群多样性和结构的影响。方法 选取SPF级雌性C57BL/6J小鼠12只,随机分为CFA组和Mock组,每组6只;Mock组右后足底皮下注射50μl的0.9%氯化钠溶液,CFA组右后足底皮下注射50μl的CFA作为慢性炎性疼痛模型组。2周后,安乐死小鼠,解剖后取结肠内粪便,组内两只小鼠结肠内粪便进行混样,采用16S rRNA高通量基因测序技术检测分析肠道菌群多样性和结构。结果 两组小鼠在肠道菌群构成上差异明显。与Mock组相比,CFA组肠道菌群丰富度及多样性降低;门水平上,厚壁菌门和TM7丰度升高;科、属水平上,气球菌属、乳酸杆菌属和脱硫弧菌属丰度显著升高,嗜冷杆菌属、普雷沃氏菌属、颤螺菌属和双歧杆菌属丰度明显降低;从门到属主要分类等级上,发现的生物标志物较多。结论 慢性炎性疼痛的小鼠肠道菌群结构尤其是优势菌群结构发生了明显变化,这些数据可为慢性炎性疼痛导致的微生态失衡的治疗及通过“肠-脑轴”改善患者消极情绪提供依据。  相似文献   
10.
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