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排序方式: 共有293条查询结果,搜索用时 15 毫秒
1.
目的研究 1型蛋白磷酸酶骨骼肌特异的糖原靶向调节亚单位基因 (PPP1R3) Asp90 5 Tyr多态性与安徽汉族人 2型糖尿病 (T2 DM)相关性。方法选取安徽省合肥地区汉族 T2 DM患者 2 6 2例 ,健康成人 10 4例 ,运用聚合酶链反应限制性酶切片段长度多态性技术 (PCR- RFL P)进行基因型测定。以体质指数 (BMI) 2 5为分割点 ,将病例组和对照组进行分层分析。结果 1PPP1R3基因 Asp90 5 Tyr多态性与安徽汉族人 2型糖尿病没有明显的相关性。 2以 BMI<2 5基因型Tyr/ Tyr组为参照组 ,BMI≥ 2 5携有 Asp90 5等位基因个体的糖尿病发病风险明显增加 (OR=3.6 9;95 % CI:1.38~ 8.89;P=0 .0 0 6 )。结论 PPP1R3基因 Asp 90 5 Tyr多态性可能不是安徽省汉族人 2型糖尿病主要的致病因素。肥胖与 Asp90 5等位基因间的交互作用可增加糖尿病的发病风险。 相似文献
2.
《Drug testing and analysis》2017,9(5):778-787
This article reports on the analytical properties of five pyrrolidinyl substituted cathinones: α ‐pyrrolidinononaphenone (α ‐PNP, 1 ), 4‐chloro‐α ‐pyrrolidinopropiophenone (4‐Cl‐α ‐PPP, 2 ), 4‐chloro‐α ‐pyrrolidinovalerophenone (4‐Cl‐α ‐PVP, 3 ), 5‐dihydrobenzofuranpyrovalerone (5‐DBFPV, 4 ), and 2‐(pyrrolidin‐1‐yl)‐1‐(5,6,7,8‐tetrahydronaphthalen‐2‐yl)hexan‐1‐one (β ‐THNPH, 5 ). These identifications were based on liquid chromatography–quadrupole time‐of‐flight‐mass spectrometry (LC–QTOF–MS), gas chromatography–mass spectrometry (GC–MS) and nuclear magnetic resonance spectroscopy (NMR). To our knowledge, no analytical data about α ‐PNP, 4‐Cl‐α ‐PPP, 4‐Cl‐α ‐PVP, and β ‐THNPH have appeared until now, making this the first report on these compounds. Moreover, in order to study the collision‐induced dissociation (CID) characteristic fragmentation routes of pyrrolidinyl substituted cathinones, a total number of 13 pyrrolidinyl substituted cathinones were selected and discussed. The major fragmentation pathways under CID mode are produced, leading to the formation of characteristic ions. Product ions of [M‐C4H9N]+ and CnH2nN+ indicate the presence of pyrrolidinyl substitution. Characteristic fragments are also produced via the cleavages of the CH–N(CH2)4 bond and the CO‐CHN bond. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献
3.
Cancer cells undergo genetic changes allowing their adaptation to environmental changes, thereby obtaining an advantage during the long metastatic route, disseminated of several changes in the surrounding environment. In particular, plasticity in cell motility, mainly due to epigenetic regulation of cancer cells by environmental insults, engage adaptive strategies aimed essentially to survive in hostile milieu, thereby escaping adverse sites. This review is focused on tumor microenvironment as a collection of structural and cellular elements promoting plasticity and adaptive programs. We analyze the role of extracellular matrix stiffness, hypoxia, nutrient deprivation, acidity, as well as different cell populations of tumor microenvironment. 相似文献
4.
Jie Liu Yong Wang Yaoyun Liao Ying Zhou Jijin Zhu 《The Journal of international medical research》2021,49(3)
ObjectivePorphyromonas gingivalis (Pg) plays a critical role in the occurrence and development of atherosclerosis. Lipopolysaccharide from Pg (Pg-LPS) could lead to pyroptosis of vascular smooth muscle cells (VSMCs) and induce instability of atherosclerotic plaque. Therefore, pyroptosis of VSMCs could promote the process of atherosclerosis. However, the exact mechanism of Pg-LPS-induced pyroptosis of VSMCs is unclear.MethodsWe determined pyroptosis and expression of interleukin (IL)-1β and IL-18 in VSMCs using 4′,6-diamidino-2-phenylindole staining and ELISA after stimulation by Pg-LPS. We established a knockdown plasmid containing the circular (circ)RNA PPP1CC and transfected it into VSMCs. Luciferase assays were performed to reveal the association between microRNAs miR-103a-3p and miR-107 and circRNA PPP1CC.ResultsStimulation of Pg-LPS led to pyroptosis of VSMCs. Knockdown of circRNA PPP1CC relieved the Pg-LPS-induced pyroptosis of VSMCs and suppressed the expression of HMGB1, TLR9, AIM2, and cleaved caspase-1. Luciferase assays showed that PPP1CC directly targeted and competitively adsorbed miR-103a-3p and miR-107, weakening the inhibitory effect of these microRNAs on the expression of HMGB1.ConclusionKnockdown of circRNA PPP1CC relieved Pg-LPS-induced pyroptosis of VSMCs. Pyroptosis of VSMCs appears to promote atherosclerosis and may represent a novel therapeutic target for its treatment. 相似文献
5.
Yiming Chen Bruce E. Blough Kevin S. Murnane Clinton E. Canal 《Drug testing and analysis》2019,11(7):990-998
Synthetic cathinones (SCs) are β‐keto analogs of amphetamines. Like amphetamines, SCs target monoamine transporters; however, unusual neuropsychiatric symptoms have been associated with abuse of some SCs, suggesting SCs might possess additional pharmacological properties. We performed radioligand competition binding assays to assess the affinities of nine SCs at human 5‐HT2A receptors (5‐HT2AR) and muscarinic M1 receptors (M1R) transiently expressed in HEK293 cells. None of the SCs exhibited affinity at M1R (minimal displacement of [~Kd] [3H]scopolamine up to 10 μM). However, two SCs, α‐pyrrolidinopropiophenone (α‐PPP) and 4‐methyl‐α‐PPP, had low μM Ki values at 5‐HT2AR. In 5‐HT2AR–phosphoinositide hydrolysis assays, α‐PPP and 4‐methyl‐α‐PPP displayed inverse agonist activity. We further assessed the 5‐HT2AR functional activity of α‐PPP, and observed it competitively antagonized 5‐HT2AR signaling stimulated by the 5‐HT2R agonist (±)‐2,5‐dimethoxy‐4‐iodoamphetamine (DOI; Kb = 851 nM). To assess in vivo 5‐HT2AR activity, we examined the effects of α‐PPP on the DOI‐elicited head‐twitch response (HTR) in mice. α‐PPP dose‐dependently blocked the HTR with maximal suppression at 10 mg/kg (P < 0.0001), which is a moderate dose used in studies investigating psychostimulant properties of α‐PPP. To corroborate a 5‐HT2AR mechanism, we also tested 3,4‐methylenedioxy‐α‐PPP (MDPPP) and 3‐bromomethcathinone (3‐BMC), SCs that we observed had 5‐HT2AR Kis > 10 μM. Neither MDPPP nor 3‐BMC, at 10 mg/kg doses, attenuated the DOI HTR. Our results suggest α‐PPP has antagonist interactions at 5‐HT2AR in vitro that may translate at physiologically‐relevant doses in vivo. Considering 5‐HT2AR antagonism has been shown to mitigate effects of psychostimulants, this property may contribute to α‐PPPs unpopularity compared to other monoamine transporter inhibitors. 相似文献
6.
Yvonne P.J. Bosch Raed Al DieriHugo ten Cate Patty J. NelemansSaartje Bloemen Bas de LaatCoenraad Hemker Patrick W. WeerwindJos G. Maessen Baheramsjah Mochtar 《Thrombosis research》2014
Introduction
Patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) are susceptible to haemostatic disturbances. Monitoring the haemostatic capacity by conventional clotting tests is challenging.Materials and Methods
Thrombin generation (TG) by Calibrated Automated Thrombography, clotting tests and tissue factor pathway inhibitor (TFPI) measurements were performed to describe the relationship between haemostatic changes and alterations in these tests. Blood samples were collected before, during and after CPB. Furthermore, it was investigated whether TG measured intraoperatively, is associated with increased risk of bleeding postoperatively.Results
TG diminished significantly (p < 0.01) after heparinization in the presence and absence of platelets (37% and 50%) compared to baseline. After the start of CPB, TG elevated and persisted till the end of surgery but remained lower than preoperatively. Activated clotting time increased after heparinization and after the start of bypass compared to baseline (400% and 500%). Anti-FXa activity reduced on the start of CPB compared to the level after heparinization, to almost the baseline value following protamine reversal of heparin. The plasma levels of total and free TFPI elevated 9 and 14 fold during bypass and remained after protamine administration higher than preoperatively. Plasma D-dimer levels reduced (p < 0.01) when bypass started. However, a marked elevation was observed in the following time points. TG in platelet-rich plasma measured after heparinization and after the start of CPB associated (p < 0.05) with postoperative blood loss.Conclusions
TG can be determined during CPB despite the high heparinization level, it reflects the haemostatic capacity better than clotting-based assays and might better predict bleeding when performed intraoperatively. 相似文献7.
Roza Chaireti Rupesh Rajani Annika Bergquist Tor Melin Inga-Lill Friis-Liby Marjo Kapraali Stergios Kechagias Tomas L. Lindahl Sven Almer 《Thrombosis research》2014
Introduction
In recent years there have been increasing evidence associating liver disease with hypercoagulability, rather than bleeding. The aim of the study was to evaluate the haemostatic potential in patients with liver disease.Patients and methods
We measured thrombin generation in the presence and absence of thrombomodulin in patients with portal vein thrombosis (PVT, n = 47), Budd-Chiari syndrome (BCS, n = 15) and cirrhosis (n = 24) and compared the results to those obtained from healthy controls (n = 21). Fifteen patients with PVT and 10 patients with BCS were treated with warfarin and were compared to an equal number of patients with atrial fibrillation matched for prothrombin time-international normalized ratio. We assessed resistance to thrombomodulin by using ratios [marker measured in the presence/absence of thrombomodulin].Results
There were no differences in thrombin generation between patients on warfarin treatment and their controls. Cirrhotic patients generated more thrombin in the presence of thrombomodulin and exhibited thrombomodulin resistance compared to controls [p = 0.006 for endogenous thrombin potential (ETP) and p < 0.001 for peak thrombin and both ratios ETP and peak] and patients with non-cirrhotic PVT (p = 0.001, p = 0.006, p < 0.001, p < 0.001 for ETP, peak, ratio ETP, ratio peak, respectively). The patients with cirrhotic PVT exhibited higher ETP (p = 0.044) and peak (p = 0.02) in the presence of thrombomodulin than controls, as well as thrombomodulin resistance (ETP and peak ratios: p = 0.001).Conclusions
Hypercoagulability and thrombomodulin resistance in patients with cirrhosis were independent of the presence of splanchnic vein thrombosis. The hypercoagulability in patients with cirrhotic PVT could have implications for considering longer or more intensive treatment with anticoagulants in this group. 相似文献8.
目的 观察和比较在人肝癌与癌旁组织中蛋白磷酸酶1调节亚基16A(protein phosphatase 1 regulatory subunit 16A,PPP1R16A)基因在基因组和转录水平的差异,探讨靶向沉默PPP1R16A基因对肝癌细胞HCC LM3增殖能力的影响.方法 收集106例肝癌患者的肿瘤组织及癌旁组织,采用实时荧光定量PCR技术检测PPP1R16A基因的基因组和转录水平.体外合成PPP1R16A序列特异性小干扰RNA(siRNA),使用脂质体法转染肝癌细胞株HCC LM3.实验分si-16A组(针对PPP1R16A的特异性siRNA转染的HCC LM3细胞)、NC组(非特异性siRNA转染的HCC LM3细胞)、空白组(未转染siRNA的HCC LM3细胞),用实时荧光定量PCR检测PPP1R16A基因拷贝数和转录水平,用蛋白质印迹法检测PPP1R16A蛋白表达,用CCK-8实验、克隆形成实验检测细胞增殖和克隆形成能力,用流式细胞术检测细胞周期.结果 人肝癌组织中PPP1R16A基因的拷贝数和转录表达水平均高于癌旁组织(P<0.01),且两者具有相关性(P=0.015).CCK-8实验和克隆形成实验显示,转染siRNA后,si-16A组细胞增殖低于NC组和空白组(P<0.001).流式细胞术结果显示,si-16A组较NC组和空白组细胞周期被抑制.结论 肝癌组织中PPP1R16A的拷贝数发生扩增,基因转录上调.靶向沉默PPP1R16A能抑制肝癌细胞HCC LM3的增殖能力.提示PPP1R16A基因在肝癌中发挥癌基因的作用. 相似文献
9.
10.
Joseph A. Jakubowski Dominick J. Angiolillo Chunmei Zhou David S. Small Brian A. Moser Jurrien M. ten Berg Patricia B. Brown Stefan James Kenneth J. Winters David Erlinge 《Thrombosis research》2014