全文获取类型
收费全文 | 448篇 |
免费 | 42篇 |
国内免费 | 13篇 |
专业分类
耳鼻咽喉 | 5篇 |
儿科学 | 9篇 |
妇产科学 | 14篇 |
基础医学 | 15篇 |
口腔科学 | 1篇 |
临床医学 | 28篇 |
内科学 | 52篇 |
皮肤病学 | 8篇 |
神经病学 | 19篇 |
特种医学 | 7篇 |
外科学 | 153篇 |
综合类 | 33篇 |
预防医学 | 7篇 |
眼科学 | 6篇 |
药学 | 131篇 |
中国医学 | 12篇 |
肿瘤学 | 3篇 |
出版年
2023年 | 2篇 |
2022年 | 1篇 |
2021年 | 8篇 |
2020年 | 14篇 |
2019年 | 10篇 |
2018年 | 9篇 |
2017年 | 16篇 |
2016年 | 12篇 |
2015年 | 12篇 |
2014年 | 25篇 |
2013年 | 61篇 |
2012年 | 24篇 |
2011年 | 22篇 |
2010年 | 30篇 |
2009年 | 31篇 |
2008年 | 25篇 |
2007年 | 35篇 |
2006年 | 40篇 |
2005年 | 41篇 |
2004年 | 32篇 |
2003年 | 14篇 |
2002年 | 16篇 |
2001年 | 12篇 |
2000年 | 6篇 |
1999年 | 4篇 |
1998年 | 1篇 |
排序方式: 共有503条查询结果,搜索用时 8 毫秒
1.
m. fox † r. sweis † t. wong † & a. anggiansah 《Neurogastroenterology and motility》2007,19(10):798-803
Oesophageal spasm presents with dysphagia and chest pain. Current treatments are limited by poor efficacy and side effects. Studies in health and oesophageal dysmotility show that sildenafil reduces peristaltic pressure and velocity; however the clinical efficacy and tolerability in symptomatic oesophageal spasm remains uncertain. We provided open-label sildenafil treatment to two patients with severe, treatment resistant symptoms associated with oesophageal spasm. The effects of sildenafil on oesophageal function and symptoms were documented by high resolution manometry (HRM). Patients were followed up to assess the efficacy of maintenance treatment with sildenafil b.i.d. HRM revealed focal and diffuse spasm in the smooth muscle oesophagus that were associated with symptoms in both cases, especially on swallowing solids. Lower oesophageal sphincter function was normal. A therapeutic trial of 25-50 mg sildenafil suppressed oesophageal contraction almost completely for water swallows; however effective, coordinated peristalsis returned with reduced frequency of spasm for solid swallows. Dysphagia and chest pain resolved during the therapeutic trial and efficacy was maintained on maintenance treatment with 25-50 mg sildenafil b.i.d. without troublesome side effects. This report shows that sildenafil can improve oesophageal function and relieve dysphagia and chest pain in patients with oesophageal spasm in whom other treatments have failed. 相似文献
2.
3.
全面康复:勃起功能障碍治疗的新目标 总被引:1,自引:1,他引:0
5型磷酸二酯酶(PDE5)抑制剂有效改善勃起功能障碍(ED)患者的勃起功能。枸橼酸西地那非的应用范围不断扩展,肺动脉高压已成为新的适应证。临床研究发现,西地那非能改善多种血管性疾病患者的内皮功能。在ED领域的研究进展包括:动物实验发现,西地那非可以改善海绵体内皮功能,增强磷酸化内皮型一氧化氮合酶(eNOS)蛋白表达,逆转缺血或缺氧导致的海绵体内压(ICP)降低。临床研究证实,西地那非可以使50%以上ED患者阴茎勃起恢复到最充分的硬度(4级勃起);使50%以上保留神经的根治性前列腺切除术后患者勃起功能康复,自发产生足以性交的勃起;使ED患者的自尊心、自信心和性关系满意度等社会心理功能恢复正常。从勃起功能到社会心理功能的全面恢复可能成为今后ED治疗的新目标。 相似文献
4.
Weiske WH 《Andrologia》1999,31(Z1):95-97
Diagnosis of erectile dysfunction is important because sildenafil may not be the proper therapy for patients with underlying major diseases such as coronary sclerosis, arteriosclerosis of the stroke vessels, depression, etc., where erectile dysfunction is just a symptom of the disease. 相似文献
5.
6.
Jane L Roberts Laurence Booth Adam Conley Nichola Cruickshanks Mark Malkin Rakesh C Kukreja Steven Grant Andrew Poklepovic Paul Dent 《Cancer biology & therapy》2014,15(6):758-767
We determined whether clinically relevant phosphodiesterase 5 (PDE5) inhibitors interacted with clinically relevant chemotherapies to kill medulloblastoma cells. In medulloblastoma cells PDE5 inhibitors interacted in a greater than additive fashion with vincristine/etoposide/cisplatin to cause cell death. Knockdown of PDE5 expression recapitulated the combination effects of PDE5 inhibitor drugs with chemotherapy drugs. Expression of dominant negative caspase 9 did not significantly inhibit chemotherapy lethality but did significantly reduce enhanced killing in combination with the PDE5 inhibitor sildenafil. Overexpression of BCL-XL and c-FLIP-s suppressed individual and combination drug toxicities. Knockdown of CD95 or FADD suppressed drug combination toxicity. Treatment with PDE5 inhibitors and chemotherapy drugs promoted autophagy which was maximal at ~12 h post-treatment, and in a cell type-dependent manner knockdown of Beclin1 or ATG5 either suppressed or enhanced drug combination lethality. PDE5 inhibitors enhanced the induction of chemotherapy-induced DNA damage in a nitric oxide synthase-dependent fashion. In conclusion, our data demonstrate that the combination of PDE5 inhibitors with standard of care chemotherapy agents for medulloblastoma represents a possible novel modality for future treatment of this disease. 相似文献
7.
Xu-Jun Xuan Gang Bai Cai-Xia Zhang Chao Xu Fu-Ding Lu Yang Peng Gang Ma Cong-Hui Han Jun Chen 《Asian journal of andrology》2016,18(1):118-122
We aim to investigate the correlations between hemodynamic parameters, penile rigidity grading, and the therapeutic effects of phosphodiesterase type 5 inhibitors using color Doppler flow imaging after intracavernosal injection in patients with erectile dysfunction. This study involved 164 patients. After intracavernosal injection with a mixture of papaverine (60 mg), prostaglandin E1 (10 μg), and lidocaine (2%, 0.5–1 ml), the penile vessels were assessed using color Doppler flow imaging. Penile rigidity was classified based on the Erection Hardness Score system as Grades 4, 3, 2 or 1 (corresponding to Schramek Grades V to II). Then, the patients were given oral sildenafil (50–100 mg) and scored according to the International Index of Erectile Function (IIEF-5) questionnaire. The number of patients with penile rigidities of Schramek Grades II to V was 14, 18, 21, and 111, respectively. The IIEF-5 score was positively correlated with the refilling index of the penile cavernosal artery (r = 0.79, P < 0.05), the peak systolic velocity (r = 0.45, P < 0.05), and penile rigidity (r = 0.75, P < 0.05), and was negatively correlated with the end diastolic velocity (r = −0.74, P < 0.05). For patients with erectile dysfunction, both the IIEF-5 score after sildenafil administration, which is correlated with penile rigidity, and the hemodynamic parameters detected using color Doppler flow imaging may predict the effects of phosphodiesterase type 5 inhibitor treatment and could provide a reasonable model for the targeted-treatment of erectile dysfunction. 相似文献
8.
U. Gómez-Pinedo R. Rodrigo O. Cauli S. Herraiz J.-M. Garcia-Verdugo B. Pellicer A. Pellicer V. Felipo 《Neuroscience》2010
During brain development neural stem cells may differentiate to neurons or to other cell types. The aim of this work was to assess the role of cGMP (cyclic GMP) in the modulation of differentiation of neural stem cells to neurons or non-neuronal cells. cGMP in brain of fetuses was reduced to 46% of controls by treating pregnant rats with nitroarginine-methylester (l-NAME) and was restored by co-treatment with sildenafil.Reducing cGMP during brain development leads to reduced differentiation of stem cells to neurons and increased differentiation to non-neuronal cells. The number of neurons in the prefrontal cortex originated from stem cells proliferating on gestational day 14 was 715±14/mm2 in control rats and was reduced to 440±29/mm2 (61% of control) in rats treated with l-NAME. In rats exposed to l-NAME plus sildenafil, differentiation to neurons was completely normalized, reaching 683±11 neurons/mm2. In rats exposed to sildenafil alone the number of cells labelled with bromodeoxyuridine (BrdU) and NeuN was 841±16/mm2. In prefrontal cortex of control rats 48% of the neural stem cells proliferating in gestational day 14 differentiate to neurons, but only 24% in rats exposed to l-NAME. This was corrected by sildenafil, 40% of cells differentiate to neurons. Similar results were obtained for neurons proliferating during all developmental period. Treatment with l-NAME did not reduce the total number of cells labelled with BrdU, further supporting that l-NAME reduces selectively the differentiation of stem cells to neurons. Similar results were obtained in hippocampus. Treatment with l-NAME reduced the differentiation of neural stem cells to neurons, although the effect was milder than in prefrontal cortex. These results support that cGMP modulates the fate of neural stem cells in brain in vivo and suggest that high cGMP levels promote its differentiation to neurons while reduced cGMP levels promote differentiation to non-neuronal cells. 相似文献
9.
Dayimi Kaya Cem Guler Ali Metin Esen Irfan Barutcu Cetin Dincel 《Annals of noninvasive electrocardiology》2004,9(3):228-233
Background: Sildenafil citrate may have direct cardiac electrophysiological effects, and is possibly responsible for some cardiac events. The aim of our study was to investigate the effects of sildenafil citrate on QT dynamicity properties with a new QT analysis program showing even small changes in ventricular repolarization. Methods: Twenty‐four‐hour Holter electrocardiographic recordings were used to obtain the data in the predrug phase (1‐hour rest position before drug administration), and in the postdrug phase (1‐hour rest position, which began 60 minutes after 50 mg oral sildenafil citrate administration). With the special QT analysis program (Verda, Reynolds Medical Ltd., UK); mean values of RR, QT, QTo (corrected QT), J (the exponent of correction formula) and S (QT/RR plots slope) parameters together with QT variability indexes (QTVI) were calculated for study phases. Results: Mean ± SEM values for RR and QT were higher in postdrug phase than in predrug phase (RR: 845 ± 42 ms vs 816 ± 46 ms, P < 0.05; QT: 371 ± 8 ms vs 361 ± 9 ms, P < 0.05). However, sildenafil did not induce any significant change in mean ± SEM values for QTo, J, and S in postdrug phase compared with predrug phase (408 ± 10 ms vs 406 ± 8 ms, 0.474 ± 0.030 vs 0.433 ± 0.025, 0221 ± 0.020 vs 0.198 ± 0.017, respectively; P > 0.05). QTVIs were also not different in each phase (predrug: ?0.874 ± 0.071 vs postdrug: ?0.997 ± 0.067, P = 0.109). Conclusions: Fifty milligrams sildenafil does not affect QT dynamicity properties. The cardiac events associated with sildenafil could not be explained with ventricular arrhythmias. 相似文献
10.
目的探讨西地那非抗低氧刺激的人肺动脉平滑肌细胞(pulmonary artery smooth muscle cells,PASMCs)增殖的机制与电压依赖性钾通道(voltage-dependent potassium channels,Kv)及环鸟甘酸依赖性蛋白激酶(cGMP-dependent protein kinase,PKG)的关系。方法采用MTT法及细胞免疫荧光法等检测细胞增殖情况;应用膜片钳技术记录低氧刺激PASMCs前后及西地那非或KT-5823干预前后的Kv通道电流,运用Kv1.5抗体透析细胞后的Kv通道电流;应用siRNA干扰技术沉默Kv1.5基因。结果低氧下西地那非组的细胞增殖水平较低氧对照组明显降低;西地那非反转了低氧对细胞K +通道电流,尤其Kv1.5通道电流的降低作用;siRNA组的Kv1.5蛋白表达明显减低,沉默Kv1.5通道基因逆转了西地那非抗低氧刺激的细胞增殖作用;PKG抑制剂KT-5823阻断了西地那非抗低氧刺激的细胞增殖作用,并且反转了西地那非对低氧下的Kv通道电流的上调作用。 结论 西地那非可通过上调Kv通道亚型主要是Kv1.5通道,抑制低氧刺激的人PASMCs增殖,且可能与PKG有关。 相似文献