全文获取类型
收费全文 | 47669篇 |
免费 | 3800篇 |
国内免费 | 1411篇 |
专业分类
耳鼻咽喉 | 189篇 |
儿科学 | 889篇 |
妇产科学 | 992篇 |
基础医学 | 4591篇 |
口腔科学 | 898篇 |
临床医学 | 5573篇 |
内科学 | 10355篇 |
皮肤病学 | 310篇 |
神经病学 | 785篇 |
特种医学 | 605篇 |
外国民族医学 | 11篇 |
外科学 | 1972篇 |
综合类 | 7166篇 |
现状与发展 | 9篇 |
预防医学 | 6202篇 |
眼科学 | 166篇 |
药学 | 6287篇 |
13篇 | |
中国医学 | 1572篇 |
肿瘤学 | 4295篇 |
出版年
2024年 | 123篇 |
2023年 | 662篇 |
2022年 | 1691篇 |
2021年 | 2092篇 |
2020年 | 1602篇 |
2019年 | 1544篇 |
2018年 | 1577篇 |
2017年 | 1512篇 |
2016年 | 1830篇 |
2015年 | 2027篇 |
2014年 | 3199篇 |
2013年 | 3867篇 |
2012年 | 3382篇 |
2011年 | 3559篇 |
2010年 | 2731篇 |
2009年 | 2493篇 |
2008年 | 2636篇 |
2007年 | 2576篇 |
2006年 | 2200篇 |
2005年 | 1893篇 |
2004年 | 1577篇 |
2003年 | 1201篇 |
2002年 | 966篇 |
2001年 | 869篇 |
2000年 | 692篇 |
1999年 | 594篇 |
1998年 | 485篇 |
1997年 | 458篇 |
1996年 | 386篇 |
1995年 | 305篇 |
1994年 | 294篇 |
1993年 | 225篇 |
1992年 | 220篇 |
1991年 | 185篇 |
1990年 | 136篇 |
1989年 | 136篇 |
1988年 | 92篇 |
1987年 | 106篇 |
1986年 | 68篇 |
1985年 | 118篇 |
1984年 | 82篇 |
1983年 | 49篇 |
1982年 | 77篇 |
1981年 | 58篇 |
1980年 | 55篇 |
1979年 | 42篇 |
1978年 | 27篇 |
1977年 | 37篇 |
1976年 | 38篇 |
1975年 | 26篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
21.
Phenotypic and genetic features of enteropathogenic Escherichia coli isolates from diarrheal children in the Ribeirão Preto metropolitan area,São Paulo State,Brazil 下载免费PDF全文
André Pitondo‐Silva Gerson Nakazato Juliana P. Falcão Kinue Irino Roberto Martinez Ana Lúcia C. Darini Rodrigo Tavanelli Hernandes 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2015,123(2):128-135
This study was designed to characterize a collection of 60 enteropathogenic Escherichia coli (EPEC) isolates from diarrheic feces of patients in the Ribeirão Preto metropolitan area regarding different phenotypic and molecular features. We examined antibiotic resistance profiles, occurrence of virulence factors‐encoding genes, intimin subtypes and the correlation of serotypes among typical (tEPEC) and atypical (aEPEC) EPEC isolates. The results demonstrated that atypical EPEC was more heterogeneous than typical EPEC concerning the characteristics investigated and 45.2% do not belong to classical EPEC serogroups. Intimin subtype β was the most frequent among the EPEC isolates (46.7%), being detected in both tEPEC and aEPEC. The majority of aEPEC isolates presented localized adherence‐like (LAL) pattern to HEp‐2 cells, although aEPEC isolates displaying diffuse adherence (DA) or non‐adherent were also detected. High prevalence of antimicrobial resistance was found for ampicillin, cephalothin, sulfonamide and tetracycline. In general, tEPEC isolates were more resistant to the antimicrobials tested than aEPEC isolates. 相似文献
22.
目的探讨依维莫司联合全反式维甲酸(简称维甲酸)逆转急性早幼粒细胞白血病(APL)细胞株NB4-R1耐药的作用。方法应用CD11b染色流式细胞术及硝基四唑氮蓝(NBT)还原实验检测两药联合应用对细胞分化的影响, 流式细胞术检测细胞周期情况, Annexin V/PI双染色检测细胞凋亡情况, 蛋白质印迹法检测自噬相关蛋白微管结合蛋白轻链3(LC3)、Beclin 1及早幼粒白血病-维甲酸受体融合蛋白(PML-RARα)、磷酸化核糖体S6激酶(P-P70S6K)、磷酸化4E结合蛋白1(P-4E-BP1) 等表达水平。结果与维甲酸组比较, 联用组能诱导耐药细胞株NB4-R1细胞的分化, 并将细胞增殖阻止在G 1期而对细胞凋亡无明显影响。100 nmol/L依维莫司组、1μmol/L维甲酸组、联用组、对照组NB4-R1细胞培养48 h后分化百分率分别为(2.29±0.57)%、(17.06±2.65)%、(54.47±4.91)%、(2.54±0.53)%; 处于G 1期的细胞百分率分别为(35.20±11.97)%、(33.54±6.25)%、(53.70±8.73)%、(27.40±6.01)%; 四组细胞凋亡细胞百分率分别为(2.30±0.14)%、(2.25±0.21)%、(2.40±0.28)%、(1.95±0.07)%。与维甲酸组比较, 联用组mTOR信号通路下游的P70S6K、4E-BP1分子磷酸化水平下降, LC3-II和Beclin 1的表达上调, 且能部分降解融合蛋白PML-RARα。 结论依维莫司联合维甲酸能诱导NB4-R1细胞分化, 且能阻滞细胞周期而不致细胞凋亡, 其机制可能与依维莫司联合维甲酸抑制mTOR信号通路激活自噬作用从而降解PML-RARα蛋白有关。 相似文献
23.
目的分析真菌性血流感染的病原菌分布以及耐药特征,为真菌血流感染的早期合理用药提供理论依据。
方法回顾性分析武汉大学人民医院2016年1月至2018年12月收治的真菌性血流感染者的菌群、科室分布以及耐药性。
结果入组192例真菌血流感染者的血培养样本中共分离192株真菌,其中白色念珠菌检出率为31.77%(61/192),其次热带念珠菌检出率为18.75%(36/192);重症医学科检出率最高为33.85%(65/192)。所有菌株均对两性霉素B敏感,对其他抗菌药物耐药率分别为5-氟胞嘧啶4.49%(9/192)、伊曲康唑5.73%(11/192)、氟康唑10.94%(21/192)和伏立康唑11.46%(22/192);除两性霉素B外,2016至2018年真菌对其他抗菌药物的耐药率均逐年上升,其中2018年所分离192株光滑念珠菌对伊曲康唑耐药菌率达46.7%。
结论真菌血流感染病原菌以念珠菌属为主,对目前抗真菌药物具有较高敏感性,但耐药率逐年上升,加强监测血培养病原菌变化及耐药趋势对指导临床用药至关重要。 相似文献
24.
James L. Dorling Alice E. Thackray James A. King Andrea Pucci Fernanda R. Goltz Rachel L. Batterham David J. Stensel 《Nutrients》2020,12(12)
The fat mass and obesity-associated gene (FTO) rs9939609 A-allele is linked to obesity and dyslipidemia, yet the independent influence of this polymorphism on blood lipids remains equivocal. We examined the influence of the FTO rs9939609 polymorphism on fasting and postprandial blood lipids in individuals homozygous for the risk A-allele or T-allele with similar anthropometric and demographic characteristics. 12 AA and 12 TT males consumed a standardized meal after fasting overnight. Blood samples were collected at baseline (−1.5 h), before the meal (0 h), and for five hours postprandially to measure lipid, glucose, and insulin concentrations. Time-averaged total area under the curve (TAUC) values (0–5 h) were calculated and compared between genotypes. Fasting triacylglycerol (TG), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, non-esterified fatty acid (NEFA), glucose, and insulin concentrations were similar between groups (p ≥ 0.293). TAUC for TG was similar in AAs and TTs (95% confidence interval (CI) −0.52 to 0.31 mmol/L/h; p = 0.606). Likewise, TAUC values were similar for NEFA (95% CI −0.04 to 0.03 mmol/L/h; p = 0.734), glucose (95% CI −0.41 to 0.44 mmol/L/h; p = 0.951), and insulin (95% CI −6.87 to 2.83 pmol/L/h; p = 0.395). Blood lipids are not influenced by the FTO rs9939609 polymorphism, suggesting the FTO-dyslipidemia link is mediated by adiposity and weight management is important in preventing FTO-related lipid variations. 相似文献
25.
Diabetes mellitus(DM) negatively affects the development and progression of chronic liver diseases(CLD) of various etiologies. Concurrent DM and CLD are also associated with worse clinical outcomes with respect to mortality, the occurrence of hepatic decompensation, and the development of hepatocellular carcinoma(HCC). Unfortunately, early diagnosis and optimal treatment of DM can be challenging, due to the lack of established clinical guidelines as well as the medical complexity of this patient population. We conducted an exploratory review of relevant literature to provide an up-to-date review for internists and hepatologists caring for this patient population. We reviewed the epidemiological and pathophysiological associations between DM and CLD, the impact of insulin resistance on the progression and manifestations of CLD, the pathogenesis of hepatogenic diabetes, as well as the practical challenges in diagnosis and monitoring of DM in this patient population. We also reviewed the latest clinical evidence on various pharmacological antihyperglycemic therapies with an emphasis on liver disease-related clinical outcomes. Finally, we proposed an algorithm for managing DM in patients with CLD and discussed the clinical and research questions that remain to be addressed. 相似文献
26.
《Joint, bone, spine : revue du rhumatisme》2019,86(3):335-341
ObjectiveRetinol-binding protein 4 (RBP4), systemic inflammation and insulin resistance (IR) are linked, yet the determinants of RBP4 and its impact on IR in rheumatoid arthritis (RA) are incompletely understood. The aim of this study was to explore the prevalence of IR in RA and investigate whether the serum levels of RBP4 were associated with IR in patients with RA.MethodsIn this study, 403 individuals with newly diagnosed and untreated RA were consecutively recruited. We calculated the Disease Activity Score assessed using 28-joint counts for swelling and tenderness (DAS28). Levels of serum RBP4, interleukin-6 (IL-6) and tumor necrosis factor (TNF) α were tested. IR was defined as Homeostasis model assessment for insulin resistance (HOMA-IR) index greater than or equal 2.40.ResultsIn those 403 patients, 68 (16.9%) were male and the median age was 43 years (IQR: 36–52). There was an evidently positive correlation between increased serum levels of RBP4 and increasing severity of RA (DAS28) (r = 0.403, P < 0.001). Furthermore, a modest positive correlation between levels of serum RBP4 and HOMA-IR score (r = 0.251; P < 0.0001) was found. Eighty-five patients (21.1%) in patients with RA were defined as IR (HOMA-IR ≥ 2.40), which was significantly higher than in normal cases (4.7%). In the patients with IR, serum levels of RBP4 were higher when compared with those in patients free-IR P < 0.001. The IR distribution across the quartiles of RBP4 ranged between 5.0% (first quartile) to 39.0% (fourth quartile), P for trend < 0.001. For each 1unit increase of RBP4, the unadjusted and adjusted risk of IR increased by 8% (OR: 1.08; 95% CI: 1.05–1.11, P < 0.001) and 5% (1.05; 1.02–1.09, P = 0.001), respectively. When RBP4 was added to the model containing established significant risk factors, AUROC (standard error) was increased from 0.768 (0.025) to 0.807(0.021). A significant difference in the AUC between the established risk factors alone and the addition of RBP4 was observed (difference, 0.039[0.004]; P = 0.02).ConclusionElevated serum levels of RBP4 were associated with increased risk of IR and might be useful in identifying RA at risk for IR and/or impaired glucose tolerance for early prevention strategies, especially in obese and women patients 相似文献
27.
28.
Auda A. Eltahla Fabio Luciani Peter A. White Andrew R. Lloyd Rowena A. Bull 《Viruses》2015,7(10):5206-5224
The hepatitis C virus (HCV) is a pandemic human pathogen posing a substantial health and economic burden in both developing and developed countries. Controlling the spread of HCV through behavioural prevention strategies has met with limited success and vaccine development remains slow. The development of antiviral therapeutic agents has also been challenging, primarily due to the lack of efficient cell culture and animal models for all HCV genotypes, as well as the large genetic diversity between HCV strains. On the other hand, the use of interferon-α-based treatments in combination with the guanosine analogue, ribavirin, achieved limited success, and widespread use of these therapies has been hampered by prevalent side effects. For more than a decade, the HCV RNA-dependent RNA polymerase (RdRp) has been targeted for antiviral development. Direct acting antivirals (DAA) have been identified which bind to one of at least six RdRp inhibitor-binding sites, and are now becoming a mainstay of highly effective and well tolerated antiviral treatment for HCV infection. Here we review the different classes of RdRp inhibitors and their mode of action against HCV. Furthermore, the mechanism of antiviral resistance to each class is described, including naturally occurring resistance-associated variants (RAVs) in different viral strains and genotypes. Finally, we review the impact of these RAVs on treatment outcomes with the newly developed regimens. 相似文献
29.
K.-C. Sung D.-C. Seo S.-J. Lee M.-Y. Lee S.H. Wild C.D. Byrne 《Nutrition, metabolism, and cardiovascular diseases : NMCD》2019,29(5):489-495
Background and aims
It is not known whether non alcoholic fatty liver disease (NAFLD) is a risk factor for diabetes in non obese, non centrally-obese subjects. Our aim was to investigate relationships between fatty liver, insulin resistance and a biomarker score for liver fibrosis with incident diabetes at follow up, in subjects who were neither obese nor centrally-obese.Methods and results
As many as 70,303 subjects with a body mass index (BMI) < 25 kg/m2 and without diabetes were followed up for a maximum of 7.9 years. At baseline, fatty liver was identified by liver ultrasound, insulin resistance (IR) by homeostatic model assessment of insulin resistance (HOMA-IR) ≥2.0, and central obesity by waist circumference (waist circumference ≥90 cm (men) and ≥85 cm (women). The Fibrosis-4 (FIB-4 score) was used to estimate extent of liver fibrosis. Cox proportional hazards models adjusted for confounders were used to estimate hazard ratios (aHRs) for incident diabetes. As many as 852 incident cases of diabetes occurred during follow up (median [IQR] 3.71 [2.03] years). Mean ± SD BMI was 22.8 ± 1.8 and 21.7 ± 2.0 kg/m2 in subjects with and without diabetes at follow up. In subjects without central obesity and with fatty liver, aHRs (95% CI) for incident diabetes at follow up were 2.17 (1.56, 3.03) for men, and 2.86 (1.50,5.46) for women. Similar aHRs for incident diabetes occurred with fatty liver, IR and the highest quartile of FIB-4 combined, in men; and there was a non significant trend toward increased risk in women.Conclusions
In normal weight, non-centrally obese subjects NAFLD is an independent risk factor for incident diabetes. 相似文献30.