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11.
目的 采用两样本孟德尔随机化研究,探索血脂水平和子宫内膜异位症之间的因果关系。方法 利用大样本全基因组关联研究(GWAS)汇总数据,选择与各类血脂水平密切相关的遗传位点为工具变量,采用逆方差加权法进行两样本孟德尔随机化分析,以OR值评价各类血脂水平与子宫内膜异位症间的因果关系。结果 除了极小极低密度脂蛋白(VLDL)胆固醇外,其余与VLDL有关的血脂水平升高会增加子宫内膜异位症的发病风险(OR>1)。高密度脂蛋白(HDL)中与胆固醇有关的血脂类型、小低密度脂蛋白(LDL)中总胆固醇水平升高可减少子宫内膜异位症的发病风险(OR<1)。所有与甘油三酯相关的血脂类型、小LDL中胆固醇酯与总脂质比率的升高均可增加子宫内膜异位症的发病风险(OR>1)。结论 多种类型的血脂水平会影响子宫内膜异位症的发生,HDL中与胆固醇或甘油三酯相关的血脂水平可作筛查子宫内膜异位症的生物指标。 相似文献
12.
Zhao Hu Feixiang Zhou Atipatsa Chiwanda Kaminga Huilan Xu 《Investigative ophthalmology & visual science》2022,63(5)
PurposeTo evaluate the potential causal associations between type 2 diabetes and fasting glucose and HbA1c levels and the risk of primary open-angle glaucoma (POAG) in European and East Asian populations.MethodsWe selected genetic variants (P < 5 × 10−8) for type 2 diabetes (898,130 Europeans; 433,540 East Asians), fasting glucose, and HbA1c (196,991 Europeans; 36,584 East Asians) from three meta-analyses of genome-wide association studies (GWAS). The GWAS for POAG provided summary statistics (192,702 Europeans; 46,523 East Asians). Mendelian randomization (MR) analysis was accomplished using the inverse variance–weighted method, weighted-median method, MR Egger method, and MR-Pleiotropy RESidual Sum and Outlier test.ResultsGenetically predicted type 2 diabetes was potentially positively associated with POAG in the European ancestry (body mass index [BMI]–unadjusted: odds ratio [OR] = 1.07, 95% confidence interval [CI], 1.01–1.14, P = 0.028; BMI-adjusted: OR = 1.07, 95% CI, 1.01–1.15, P = 0.035), but not in the East Asian ancestry (BMI-unadjusted: OR = 1.01, 95% CI, 0.95–1.06, P = 0.866; BMI-adjusted: OR = 1.00, 95% CI, 0.94–1.05, P = 0.882). There was no evidence to support a causal association of fasting glucose (European: OR = 1.19, P = 0.157; East Asian: OR = 0.94, P = 0.715) and HbA1c (European: OR = 1.27, P = 0.178; East Asian: OR = 0.85, P = 0.508) levels with POAG.ConclusionsThe causal effect of type 2 diabetes on the risk of POAG is different in European and East Asian populations. The point estimates of fasting glucose and Hb1Ac with POAG are large but not statistically significant, which prompts the question of statistical power. 相似文献
13.
Objective: Osteoporosis (OP) is the most common bone disease. The genetic and metabolic factors play important roles in OP development. However, the genetic basis of OP is still elusive. The study aimed to explore the relationships between OP and dietary habits. Methods: This study used large-scale genome-wide association study (GWAS) summary statistics from the UK Biobank to explore potential associations between OP and 143 dietary habits. The GWAS summary data of OP included 9434 self-reported OP cases and 444,941 controls, and the GWAS summary data of the dietary habits included 455,146 participants of European ancestry. Linkage disequilibrium score regression (LDSC) was used to detect the genetic correlations between OP and each of the 143 dietary habits, followed by Mendelian randomization (MR) analysis to further assess the causal relationship between OP and candidate dietary habits identified by LDSC. Results: The LDSC analysis identified seven candidate dietary habits that showed genetic associations with OP including cereal type such as biscuit cereal (coefficient = −0.1693, p value = 0.0183), servings of raw vegetables per day (coefficient = 0.0837, p value = 0.0379), and spirits measured per month (coefficient = 0.115, p value = 0.0353). MR analysis found that OP and PC17 (butter) (odds ratio [OR] = 0.974, 95% confidence interval [CI] = (0.973, 0.976), p value = 0.000970), PC35 (decaffeinated coffee) (OR = 0.985, 95% CI = (0.983, 0.987), p value = 0.00126), PC36 (overall processed meat intake) (OR = 1.035, 95% CI = (1.033, 1.037), p value = 0.000976), PC39 (spirits measured per month) (OR = 1.014, 95% CI = (1.011, 1.015), p value = 0.00153), and servings of raw vegetables per day (OR = 0.978, 95% CI = (0.977, 0.979), p value = 0.000563) were clearly causal. Conclusions: Our findings provide new clues for understanding the genetic mechanisms of OP, which focus on the possible role of dietary habits in OP pathogenesis. 相似文献
14.
采用改进模拟退火法作为人工神经网络的学习算法,提出了适用于连续型输入变量、整体优化的完全随机型神经网络,并在1,6-二磷酸果糖制备条件优化中得到了成功应用,单位体积产率显著提高,为工业化生产提供了有利条件。 相似文献
15.
目的 研究白细胞介素12受体B1基因(IL-12RB1)突变所致孟德尔遗传易感分枝杆菌病的基因资料及临床特点,提高对该病的认识。方法 检测2016—2018年中国医学科学院北京协和医院就诊的2例播散性卡介苗感染患儿基因并分析结果,同时总结患儿的临床资料。结果 2例患儿分别为11月龄和13月龄男性儿童,均于出生后接种卡介苗,接种后3个月出现同侧腋下淋巴结肿大,病原学检查提示抗酸杆菌生长。均否认结核病接触史。基因检测分析结果显示2例患儿均为IL-12RB1复合杂合基因突变,分别为c.1561C>T,p.R521X;c.632G>C,p.R211P;c.339-340 del CT,p.L113Lfs*15和c.1791+2T>G。其中c.339-340 del CT,p.L113Lfs*15未见报道,是新突变。结论 对于接种卡介苗后出现感染性播散的患儿,应进行原发性免疫缺陷基因检测,相关基因突变的识别,可为早期治疗及遗传咨询提供依据。 相似文献
16.
摘要
目的:通过采用孟德尔随机化(MR)方法和反向孟德尔随机化方法评估91种炎症蛋白与5种心血管疾病(动脉夹层、动脉瘤、冠心病、非风湿性瓣膜病和风湿性瓣膜病)之间的因果关系。
方法:使用来自欧洲人群的全基因组关联研究(GWAS)数据,利用孟德尔随机化(MR)方法和反向孟德尔随机化方法对 91 种炎症蛋白与5种心血管疾病之间的双向因果关系进行评估分析。MR分析方法包括inverse variance weighted (IVW)、Weighted median、MR-Egger、Simple Mode和Weighted mode。敏感性分析包括 Cochran''s Q 检验、MR-Egger 截距检验、MR-PRESSO 方法和 leave-one-out 方法。
结果:共有16种炎症蛋白可能与心血管疾病风险存在相关性,包括CCL20、CD5、CCL28、IL20RA、LAP-TGF-β1、TSLP、CST5、LIF、EIF4EBP1、CCL4、IL22RA1、IL-10、IL-17C、MCP-2/CCL8、NRTN和MCP-3/CCL7。此外,心血管疾病的进展可能会导致总共 10 种炎症蛋白水平的变化,包括 CCL11、IL-8、TNF-β、FGF19、IL10RA、FGF-21、IL10RB、β-NGF、CD5 和 MCP-1/CCL2。
结论:本研究结果表明,多种炎症蛋白与5种心血管疾病之间存在双向因果关系,证明了进一步研究各种炎症蛋白与上述心血管疾病之间的相关性存在更深入的研究空间。 相似文献
17.
Minhan Yi Wangcheng Zhao Yun Tan Quanming Fei Kun Liu Ziliang Chen Yuan Zhang 《Annals of medicine》2022,54(1):1578
BackgroundObstructive sleep apnea (OSA) and inflammation are closely related. This study aimed to evaluate the associations and causal effect between C-reactive protein (CRP) and tumour necrosis factor-alpha (TNF-α) levels and OSA.MethodsPooled analysis was conducted to compare the expression differences of CRP and TNF-α between OSA patients with different severity and controls, and between continuous positive airway pressure (CPAP) and non-CPAP interventions for OSA patients. Using published GWAS summary statistics, we conducted a bidirectional two-sample Mendelian Randomization (MR) to estimate the causal relationships between CRP and TNF-α levels and OSA risk. Effect estimates were evaluated using inverse-variance weighted (IVW) as primary method, and several other MR methods as sensitivity analysis.ResultsBoth TNF-α (WMD [95%CI] = 5.86 [4.80–6.93] pg/ml, p < .00001) and CRP (WMD [95%CI] = 2.66 [2.15–3.17] mg/L, p < .00001), showed a significant increase in OSA patients compared with controls and this increasing trend was associated with OSA severity. Besides, compared to blank control (non-CPAP), CPAP treatment can reduce high TNF-α (WMD [95%CI]= −4.44 [−4.81, −4.07]pg/ml, p < .00001) and CRP (WMD [95%CI]= −0.91 [−1.65, −0.17] mg/l, p = .02) in OSA. Moreover, the primary MR analysis by IVW showed that OSA was the genetically predicted cause of elevated CRP (estimate: 0.095; 95% CI, [0.010–0.179]; p = .029) using six SNPs as the instrument variable, which were repeated by weighted median (estimate: 0.053; 95% CI, [0.007, 0.100]; p =.024) and MR RAPS (estimate: 0.109; 95% CI, [0.079, 0.140]; p = 1.98x10−12). Besides, the causal effect from elevated CRP on increased OSA risk was almost significant by IVW (OR:1.053; 95% CI, [1.000, 1.111]; p = .053). However, there were no causal associations between TNF-α and OSA from both directions.ConclusionsIncreased CRP and TNF-α were associated with OSA severity and sensible to CPAP treatment. Also, OSA had a suggestive causal effect on elevated CRP. 相似文献
18.
PurposeIt has been found that childhood obesity (CO) may play an important role in the onset and progression of osteoarthritis (OA). Thus we conducted this mendelian randomisation analysis (MR) to evaluate the causal association between childhood obesity and osteoarthritis.MethodsInstrumental variables (IVs) were obtained from publicly available genome-wide association study datasets. The leave-one-out sensitivity test, MR Pleiotropy RESidual Sum and Outlier test (MR-PRESSO), and Cochran’s Q test were used to confirm the heterogeneity and pleiotropy of identified IVs, then five different models, including the inverse variance weighted model (IVW), weighted median estimator model (WME), weighted model-based method (WM), MR-Egger regression model (MER), and MR-Robust Adjusted Profile Score (MRAPS) were applied in this MR analysis.ResultsAfter excluding all outliers identified by the MR-PRESSO test, no evident directional pleiotropy was found. Significant heterogeneity was found in the secondary MR and as a result, the multiplicative random-effect model was used. Significant causal association between CO and OA (OR 1.0075, 95% CI [1.0054, 1.0010], p = 8.12 × 10−13). The secondary MR also revealed that CO was causally associated with knee OA (OR 1.1067, 95% CI [1.0769, 1.1373], p = 3.30 × 10−13) and hip OA (OR 1.1272, 95% CI [1.0610, 1.1976], p = 1.07 × 10−4). The accuracy and robustness of these findings were confirmed by sensitivity tests.ConclusionThere appears to be a causal relationship between childhood obesity and OA. Our results indicate that individuals with a history of childhood obesity require specific clinical attention to prevent the development of knee and hip OA. 相似文献
19.
20.
目的 采用孟德尔随机化(MR)方法探索睡眠性状与肠易激综合征(IBS)的因果关系。方法 利用大规模全基因组关联研究汇总数据和芬兰生物银行数据(FinnGen),选择相互独立且与睡眠性状密切相关的遗传位点作为工具变量,通过逆方差加权法(MR-IVW)、加权中位数法、简单中位数法、稳健的调整轮廓评分法、MR多效性残差和与异质性法(MR-PRESSO)等MR方法,以比值比(OR值)作为评价指标对睡眠性状与IBS的因果关系进行探讨。结果 MR-IVW结果显示,过短睡眠和失眠分别导致IBS发病风险增高147%(OR=2.47, 95%CI:1.13~5.41)和18%(OR=1.18, 95%CI:1.14~1.22),早起型睡眠习惯会导致IBS发病风险降低12%(OR=0.88, 95%CI:0.84~0.92)。外部数据验证结果显示,仅失眠与IBS发病风险的关联有统计学意义(P<0.001)。多变量MR方法校正相关协变量后,失眠与IBS的关联效应仍有统计学意义(P<0.001)。结论 过短睡眠和失眠会增加IBS的发病风险。 相似文献