全文获取类型
收费全文 | 530篇 |
免费 | 68篇 |
国内免费 | 5篇 |
出版年
2024年 | 3篇 |
2023年 | 11篇 |
2022年 | 11篇 |
2021年 | 15篇 |
2020年 | 16篇 |
2019年 | 22篇 |
2018年 | 16篇 |
2017年 | 22篇 |
2016年 | 19篇 |
2015年 | 34篇 |
2014年 | 39篇 |
2013年 | 80篇 |
2012年 | 29篇 |
2011年 | 45篇 |
2010年 | 25篇 |
2009年 | 21篇 |
2008年 | 29篇 |
2007年 | 26篇 |
2006年 | 27篇 |
2005年 | 9篇 |
2004年 | 24篇 |
2003年 | 9篇 |
2002年 | 13篇 |
2001年 | 4篇 |
2000年 | 5篇 |
1999年 | 3篇 |
1998年 | 1篇 |
1997年 | 6篇 |
1996年 | 9篇 |
1995年 | 4篇 |
1994年 | 4篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 4篇 |
1989年 | 2篇 |
1987年 | 3篇 |
1986年 | 1篇 |
1984年 | 3篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1975年 | 1篇 |
排序方式: 共有603条查询结果,搜索用时 15 毫秒
221.
Drugs that interact with cardiac electro-mechanics: old and new targets for treatment 总被引:1,自引:1,他引:0
Kirchhof P Fortmüller L Waldeyer C Breithardt G Fabritz L 《Progress in biophysics and molecular biology》2008,97(2-3):497-512
The concept of mechano-electrical feedback was derived from the observation that a short stretch applied to the beating heart can invoke an electrical response in the form of an afterdepolarization or a premature ventricular beat. More recent work has identified stretch-activated channels whose specific inhibition might help to treat atrial fibrillation in the near future. But the interaction between electrical and mechanical function of the heart is a continuum from short-term (within milliseconds) to long-term (within weeks or months) effects. The long-term effects of pressure overload have been well-described on the molecular and cellular level, and substances that interact with these processes are used in clinical routine in the care of patients with cardiac hypertrophy and heart failure. These treatments help to prevent lethal arrhythmias (sudden death) and potentially atrial fibrillation. The intermediate interaction between mechanical and electrical function of the heart is less well-understood. Several recently identified regulatory mechanisms may provide novel antiarrhythmic targets associated with the "intermediate" response of the myocardium to stretch. 相似文献
222.
OBJECTIVE: To examine the relation of the single nucleotide polymorphisms (SNPs) of the resistin gene on the plasma resistin concentration and cardiovascular risk factors. METHODS AND RESULTS: Plasma resistin concentrations were measured and SNP -420C>G, +157C>T, and +299G>A genotyped in our Finnish population-based cohort. Association analyses were performed in the control group of the cohort (n=515). In addition, the hypertension group (n=505), representing a high-risk group, was analyzed for these SNP's and the frequencies were compared with the low-risk control group. Resistin concentration differed significantly between the SNP genotypes, the common homozygotes having the lowest concentration in every SNP (p<0.01). After adjustment for age, sex, and BMI SNP -420C-C homozygotes had the lowest IGFBP-1 (p=0.001), the highest GHbA(1c) (p=0.028) in all the subjects and the lowest quick index (p<0.001) and the highest insulin (p<0.001) among female subjects of the control cohort. Plasma triglycerides were the lowest among G-G homozygotes (p=0.006). In addition, the SNP -420C allele was more frequent among hypertensive than control cohort (p=0.018). CONCLUSIONS: The results imply that genetic variation seems to have a role in the determination of plasma resistin level. SNP -420C-C homozygozity status seems to be associated with more deleterious metabolic profile. 相似文献
223.
Bone marrow derived-mesenchymal stem cells (BM-MSCs) have brought great attention in regenerative medicine field, various experimental & clinical trials were held to investigate their therapeutic effects in different disorders. We designed a histological & immunohistochemical study to evaluate effectiveness of MSCs therapy in withhold of end-stage renal disease (ESRD) secondary to hypertension which has become a growing & striking public health problem. 30 adult male albino rats were utilized, 20 of them were exposed to experimental induction of hypertension, then divided equally to MSCs treated group (injected with 1 × 106 fluorescent labeled cell i.v./rat), while the second one was left without treatment. Renal specimens were subjected to histopathological, ultrastructural and immunohistochemical examination for Nrf2 in addition to biochemical estimation of serum urea & creatinine. Our results documented that BM-derived MSCs exerts considerable reversing effect of histopathologic and ultrastructural hypertensive nephropathy. Moreover, immunohistochemical results clearly pointed to relevant role of Nrf2 pathway in MSCs related renal therapeutic effects. 相似文献
224.
目的:探讨静脉注射乌拉地尔与硝酸甘油微泵对高血压患者拔牙术中血压及心率(HR)的影响。方法:选择自2015年1月到2016年10月在我院进行心电监护拔牙的高血压患者116例纳入本次研究,根据随机数字表法将患者分成观察组以及对照组各58例,对照组给予硝酸甘油加泵静点维持,观察组给予乌拉地尔加泵静点维持,对比两组术前、麻醉时、麻醉后10min、术中及术后10min收缩压(SBP)、舒张压(DBP)以及HR的变化,并对比两组不良反应情况。结果:两组术中及术后10min的SBP和DBP水平均分别明显低于术前,观察组术中的SBP和DBP水平均分别明显低于对照组,差异均有统计学意义(P0.05);对照组术中及术后10min的HR均明显高于术前,且观察组均明显低于对照组,差异均有统计学意义(P0.05)。观察组不良反应的总发生率是6.90%(4/58),与对照组的10.34%(6/58)相比,差异无统计学意义(P0.05)。结论:静脉注射乌拉地尔对高血压患者在拔牙术中血压及HR的影响较小,安全性较好,值得推广。 相似文献
225.
目的:探究氯沙坦联合麝香保心丸治疗高血压合并心衰患者的临床效果。方法:选取我院于2014年1月~2016年1月收治的152例原发性高血压合并心力衰竭患者,按照治疗方法的不同随机分为观察组和对照组,每组76例。对照组患者予以吸氧、β受体阻滞剂、利尿等常规治疗,观察组在常规治疗的基础上加用氯沙坦联合麝香保心丸治疗,比较两组患者治疗前后的血压、心功能、血清血清B型脑钠肽(BNP)及超敏C反应蛋白(hs-CRP)水平。结果:治疗后,两组患者的血压、左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)、水平和血清BNP、hs-CRP水平均较治疗前显著降低(P0.05),LVEF(%)水平较治疗前显著升高,且观察组患者的血压、LVEDD、LVESD水平和血清B型脑钠肽(BNP)、超敏C反应蛋白(hs-CRP)水平显著低于对照组(P0.05),LVEF(%)水平显著高于对照组(P0.05)。结论:氯沙坦联合麝香保心丸治疗高血压合并心衰患者的临床效果优于常规治疗,可有效控制血压并改善患者的心功能。 相似文献
226.
Brian G. Lawhorn Tritin Tran Victor S. Hong Lisa A. Morgan BaoChau T. Le Mark R. Harpel Larry Jolivette Elsie Diaz Benjamin Schwartz Jeffrey W. Gross Thaddeus Tomaszek Simon Semus Nestor Concha Angela Smallwood Dennis A. Holt Lara S. Kallander 《Bioorganic & medicinal chemistry letters》2017,27(21):4838-4843
Discovery of potent renin inhibitors which contain a simplified alkylamino Asp-binding group and exhibit improved selectivity for renin over Cyp3A4 is described. Structure-function results in this series are rationalized based on analysis of selected compounds bound to renin, and the contribution of each molecular feature leading to the reduced P450 inhibition is quantified. 相似文献
227.
Harry R. Chobanian Yan Guo Barbara Pio Haifeng Tang Nardos Teumelsan Matthew Clements Jessica Frie Ronald Ferguson Zach Guo Brande S. Thomas-Fowlkes John P. Felix Jessica Liu Martin Kohler Birgit Priest Caryn Hampton Lee-Yuh Pai Aaron Corona Joseph Metzger Alexander Pasternak 《Bioorganic & medicinal chemistry letters》2017,27(4):1109-1114
A spirocyclic class of ROMK inhibitors was developed containing a structurally diverse heterocyclic sulfone moiety and spirocyclic core starting from lead 1. These compounds not only displayed exquisite ROMK potency but significantly improved selectivity over hERG. The lead compounds were found to have favorable pharmacokinetic properties and displayed robust diuretic, natriuretic and blood pressure lowering effects in spontaneously hypertensive rats. 相似文献
228.
摘要 目的:探讨LncRNA-NEAT1对妊娠期高血压大鼠JAK2/STAT3信号通路、炎症反应和妊娠结局的影响。方法:采用注射L-精氨酸甲酯的方法构建妊娠期高血压大鼠模型。采用Western blot检测JAK2/STAT3信号通路蛋白表达;采用ELISA法检测炎症因子和血管内皮损伤因子。观察并记录大鼠24 h蛋白尿、尾静脉压和死胎率。结果:与空白组相比,模型组、LncRNA-NEAT1过表达组、LncRNA-NEAT1抑制组JAK2、STAT3的蛋白表达水平明显更高(P<0.05);与模型组相比,LncRNA-NEAT1抑制组JAK2、STAT3的蛋白表达水平明显更低(P<0.05),而LncRNA-NEAT1过表达组JAK2、STAT3的蛋白表达水平明显更高(P<0.05);与空白组相比,模型组、LncRNA-NEAT1过表达组、LncRNA-NEAT1抑制组ET-1和sICAM-1水平明显更高,而NO水平明显更低(P<0.05);与模型组相比,LncRNA-NEAT1过表达组、LncRNA-NEAT1抑制组ET-1和sICAM-1水平明显更高(P<0.05),而NO水平明显更低(P<0.05),而LncRNA-NEAT1过表达组ET-1和sICAM-1表达水平明显更高,而NO明显更低(P<0.05);与空白组相比,模型组、LncRNA-NEAT1过表达组、LncRNA-NEAT1抑制组TNF-α、IL-1β、IL-18表达水平明显更高(P<0.05);与模型组相比,LncRNA-NEAT1抑制组TNF-α、IL-1β、IL-18表达水平明显更低(P<0.05),而LncRNA-NEAT1过表达组TNF-α、IL-1β、IL-18表达水平明显更高(P<0.05);与空白组相比,模型组、LncRNA-NEAT1过表达组、LncRNA-NEAT1抑制组尾静脉压和24h蛋白尿水平明显更高(P<0.05);与模型组相比,LncRNA-NEAT1抑制组尾静脉压和24 h蛋白尿表达水平明显更低(P<0.05),而LncRNA-NEAT1过表达组尾静脉压和24 h蛋白尿表达水平明显更高(P<0.05);LncRNA-NEAT1过表达组(21.56%)死胎率显著高于模型组(16.72%)和LncRNA-NEAT1抑制组(5.65%)。结论:妊娠期糖尿病大鼠LncRNA-NEAT1的表达下调可抑制JAK2/STAT3信号通路的表达并下调下游促炎因子的表达,进而缓解血管内皮损伤降低死胎率。 相似文献
229.
Faisal Shabbir Akash PatelCharles Mattison Sumit BoseRaathathulaksi Krishnamohan Emily SweeneySarina Sandhu Wynand NelAfsha Rais Ranbir SandhuNguasaah Ngu Sushil Sharma 《Neurochemistry international》2013
Depression is characterized by sadness, purposelessness, irritability, and impaired body functions. Depression causes severe symptoms for several weeks, and dysthymia, which may cause chronic, low-grade symptoms. Treatment of depression involves psychotherapy, medications, or phototherapy. Clinical and experimental evidence indicates that an appropriate diet can reduce symptoms of depression. The neurotransmitter, serotonin (5-HT), synthesized in the brain, plays an important role in mood alleviation, satiety, and sleep regulation. Although certain fruits and vegetables are rich in 5-HT, it is not easily accessible to the CNS due to blood brain barrier. However the serotonin precursor, tryptophan, can readily pass through the blood brain barrier. Tryptophan is converted to 5-HT by tryptophan hydroxylase and 5-HTP decarboxylase, respectively, in the presence of pyridoxal phosphate, derived from vitamin B6. Hence diets poor in tryptophan may induce depression as this essential amino acid is not naturally abundant even in protein-rich foods. Tryptophan-rich diet is important in patients susceptible to depression such as certain females during pre and postmenstrual phase, post-traumatic stress disorder, chronic pain, cancer, epilepsy, Parkinson’s disease, Alzheimer’s disease, schizophrenia, and drug addiction. Carbohydrate-rich diet triggers insulin response to enhance the bioavailability of tryptophan in the CNS which is responsible for increased craving of carbohydrate diets. Although serotonin reuptake inhibitors (SSRIs) are prescribed to obese patients with depressive symptoms, these agents are incapable of precisely regulating the CNS serotonin and may cause life-threatening adverse effects in the presence of monoamine oxidase inhibitors. However, CNS serotonin synthesis can be controlled by proper intake of tryptophan-rich diet. This report highlights the clinical significance of tryptophan-rich diet and vitamin B6 to boost serotonergic neurotransmission in depression observed in various neurodegenerative diseases. However pharmacological interventions to modulate serotonergic neurotransmission in depression, remains clinically significant. Depression may involve several other molecular mechanisms as discussed briefly in this report. 相似文献
230.
本研究选取2015年6月至2017年6月我院收治的高血压脑出血患者124例,根据不同的治疗方法分为对照组和观察组。对照组患者采用常规治疗,观察组患者采用常规治疗联合微创颅内血肿清除术治疗,分析微创颅内血肿清除术对脑出血血清铁蛋白(SF)、神经营养因子(NTF)水平以及血清中炎症因子的影响及临床治疗效果。结果表明,治疗前,两组患者出血量、昏迷程度评分比较无统计学差异(p>0.05);治疗后,观察组患者出血量、昏迷程度评分低于对照组(p<0.05)。治疗前,两组患者MMP-9、SF、NTF、GFAP、TNF-α、hs-CRP水平比较无统计学差异(p>0.05);治疗后,观察组患者MMP-9、SF、NTF、GFAP、TNF-α、hs-CRP水平低于对照组(p<0.05)。治疗前,两组患者神经功能评分比较无统计学差异(p>0.05);治疗7 d、14d后,观察组患者神经功能评分低于对照组(p<0.05)。本研究的结果初步说明,微创颅内血肿清除术治疗脑出血可减少患者出血量,降低患者血清炎症因子水平及神经细胞损伤因子的表达水平,改善患者神经功能。 相似文献