全文获取类型
收费全文 | 2457篇 |
免费 | 203篇 |
国内免费 | 7篇 |
专业分类
耳鼻咽喉 | 3篇 |
儿科学 | 58篇 |
妇产科学 | 34篇 |
基础医学 | 466篇 |
口腔科学 | 32篇 |
临床医学 | 289篇 |
内科学 | 567篇 |
皮肤病学 | 67篇 |
神经病学 | 242篇 |
特种医学 | 68篇 |
外科学 | 259篇 |
综合类 | 7篇 |
一般理论 | 1篇 |
预防医学 | 139篇 |
眼科学 | 28篇 |
药学 | 161篇 |
中国医学 | 5篇 |
肿瘤学 | 241篇 |
出版年
2023年 | 29篇 |
2022年 | 43篇 |
2021年 | 97篇 |
2020年 | 55篇 |
2019年 | 92篇 |
2018年 | 99篇 |
2017年 | 62篇 |
2016年 | 74篇 |
2015年 | 73篇 |
2014年 | 128篇 |
2013年 | 135篇 |
2012年 | 245篇 |
2011年 | 238篇 |
2010年 | 137篇 |
2009年 | 113篇 |
2008年 | 162篇 |
2007年 | 179篇 |
2006年 | 168篇 |
2005年 | 147篇 |
2004年 | 136篇 |
2003年 | 98篇 |
2002年 | 75篇 |
2001年 | 4篇 |
2000年 | 3篇 |
1999年 | 7篇 |
1998年 | 26篇 |
1997年 | 6篇 |
1996年 | 4篇 |
1995年 | 4篇 |
1993年 | 3篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1986年 | 1篇 |
1984年 | 1篇 |
1980年 | 1篇 |
1977年 | 1篇 |
1976年 | 2篇 |
1974年 | 2篇 |
1973年 | 1篇 |
1972年 | 2篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1969年 | 2篇 |
1967年 | 2篇 |
1966年 | 1篇 |
1964年 | 2篇 |
1963年 | 1篇 |
1960年 | 1篇 |
1911年 | 1篇 |
排序方式: 共有2667条查询结果,搜索用时 15 毫秒
991.
In a recently published article we report the metagenomic analysis of human gut microbiomes evolved in the absence of immunoglobulin A (IgA). We show that human IgA deficiency is not associated with massive quantitative perturbations of gut microbial ecology. While our study underlines a rather expected pathobiont expansion, we at the same time highlight a less expected depletion in some typically beneficial symbionts. We also show that IgM partially supply IgA deficiency, explaining the relatively mild clinical phenotype associated with the early steps of this condition. Microbiome studies in patients should consider potential issues such as cohort size, human genetic polymorphism and treatments. In this commentary, we discuss how such issues were taken into account in our own study. 相似文献
992.
993.
Leclercq D Delmaire C de Champfleur NM Chiras J Lehéricy S 《Neurosurgery Clinics of North America》2011,22(2):253-68, ix
Diffusion tensor imaging (DTI) tractography is increasingly used in presurgical mapping in tumors located in eloquent areas since it is the only non invasive technique that permits in vivo dissection of white matter tracts. Concordance between the DTI tracts and subcortical electrical intraoperative mapping is high, and DTI tractography has proven useful to guide surgery. However, it presents limitations due to the technique and the tumor, which must be known before using the images in the operative room. This review focuses on the possibilities and limits of DTI imaging in intraoperative tumoral mapping and presents an overview of current knowledge. 相似文献
994.
Behr-Roussel D Oger S Caisey S Sandner P Bernabé J Alexandre L Giuliano F 《European urology》2011,59(2):272-279
Background
Phosphodiesterase type 5 inhibitors (PDE5-Is) improve storage symptoms in benign prostatic hyperplasia patients, despite a lack of effect on peak urinary flow rate. Moreover, vardenafil improves urodynamic parameters in spinal cord-injured (SCI) patients with neurogenic detrusor overactivity (NDO). SCI rats also display NDO characterized by nonvoiding contractions (NVCs) during bladder filling, resulting in an increased bladder afferent nerve firing (BANF).Objective
We postulated that vardenafil could improve urodynamic parameters by reducing BANF. The effect of vardenafil has been investigated on intravesical pressure by cystometry experiments while recording BANF in response to bladder filling.Design, setting, and participants
Complete T7–T8 spinalization was performed in 15 female adult Sprague-Dawley rats (250–275 g).Measurements
At 21–29 d postspinalization, fine filaments were dissected from the L6 dorsal roots and placed across a bipolar electrode. Bladder afferent nerve fibers were identified by electrical stimulation of the pelvic nerve and bladder distension. SCI rats were decerebrated before cystometry experiments. Bladders were filled to determine the maximal bladder filling volume (BFV) for each rat. Then, after bladder stabilization at 75% of maximal BFV, saline (n = 7) or vardenafil 1 mg/kg (n = 8) was delivered intravenously. NVCs and BANF were recorded for 45 min.Results and limitations
In all SCI rats, BANF was already present and regular at resting conditions (26.2 ± 4.1 spikes per second). During bladder filling, intravesical pressure (IVP) slowly increased with transient NVCs superimposed. Concomitantly, BANF progressively increased up to 2.4-fold at maximal BFV (2.08 ± 0.24 ml). After stabilization at submaximal BFV, BANF was increased by 186 ± 37%. Vardenafil injection induced an immediate decrease in NVCs compared to saline (p < 0.001) and BANF (52% decrease vs 28% in saline after 45 min; p < 0.001).Conclusions
Systemic vardenafil reduced both NVCs and BANF in unanesthetized, decerebrate, SCI rats. These findings provide new insights into the mechanism of action by which PDE5-Is improve storage symptoms in SCI patients. 相似文献995.
Le Broc-Ryckewaert D Pommery N Pommery J Ghinet A Farce A Wiart JF Gautret P Rigo B Hénichart JP 《Drug Metabolism Letters》2011,5(3):209-215
Phenstatin and its derivatives are potential anticancer drug candidates according to their inhibitory properties on tubulin polymerization, cell growth and antivascular activity. However, at the present time, neither pharmacological nor metabolic studies have been conducted in order to strengthen the relevance of phenstatine as a drug discovery candidate. In the present work, the metabolic fate of phenstatin in rat and human microsomal preparations was studied to investigate the stability of this tubulin polymerization inhibitor and any effects of the metabolites on polymerization and on PC3 cancer cell proliferation. The metabolites were separated by high-performance liquid chromatography and, after their synthesis, characterized by simultaneous LC-DAD-UV and LC-ESI-MS analyses. Thus, eight metabolites were identified. The major biotransformation pathways are carbonyl reduction, O-methylation at C-3', O-methylation after aromatic hydroxylation at the position C-2' on phenyl B ring and O-demethylation on A ring. Four of the identified metabolites were as active or more active, than phenstatin in vitro. Moreover, the better stability of phenstatin versus CA-4 and the lack of quinone formation could justify the design of new analogues which could include various substituents on phenyl rings or linker group in order to modulate the metabolism of phenstatin toward even more active metabolites and so up-regulate the pharmacological activity. 相似文献
996.
Heparin derivative-based therapy has evolved from unfractionated heparin (UFH) to low-molecular-weight heparins (LMWHs) and now fondaparinux, a synthetic pentasaccharide. Contrary to UFH or LMWHs, fondaparinux is not neutralized by protamine sulfate, and no antidote is available to counteract bleeding disorders associated with overdosing. To make the use of fondaparinux safer, we developed an antithrombin (AT) variant as a potent antidote to heparin derivatives. This variant (AT-N135Q-Pro394) combines 2 mutations: substitution of Asn135 by a Gln to remove a glycosylation site and increase affinity for heparins, and the insertion of a Pro between Arg393 and Ser394 to abolish its anticoagulant activity. As expected, AT-N135Q-Pro394 anticoagulant activity was almost abolished, and it exhibited a 3-fold increase in fondaparinux affinity. AT-N135Q-Pro394 was shown to reverse fondaparinux overdosing in vitro in a dose-dependent manner through a competitive process with plasma AT for fondaparinux binding. This antidote effect was also observed in vivo: administration of AT-N135Q-Pro394 in 2.5-fold molar excess versus plasma AT neutralized 86% of the anti-Xa activity within 5 minutes in mice treated with fondaparinux. These results clearly demonstrate that AT-N135Q-Pro394 can reverse the anticoagulant activity of fondaparinux and thus could be used as an antidote for this drug. 相似文献
997.
998.
Rénard C Barlogis V Mialou V Galambrun C Bernoux D Goutagny MP Glasman L Loundou AD Poitevin-Later F Dignat-George F Dubois V Picard C Chabannon C Bertrand Y Michel G 《British journal of haematology》2011,152(3):322-330
We report the post‐transplant lymphocyte subset recovery of 226 children treated with Unrelated Cord Blood transplant (UCBT) (n = 112) or Unrelated Bone Marrow Transplant (UBMT) (n = 114) for malignant or non‐malignant diseases. Absolute numbers of natural killer (NK), B and T cells were monitored by flow cytometry up to 5 years post‐transplant. Immunological endpoints were: time to achieve a CD3+ cell count >0·5 and 1·5 × 109/l, CD4+ > 0·2 and 0·5 × 109/l, CD8+ > 0·25 × 109/l, CD19+ > 0·2 × 109/l, NK > 0·1 × 109/l. These endpoints were analysed through the use of cumulative incidence curves in the context of competing risks. CD8+ T cell recovery was delayed after UCBT with a median time to reach CD8+ T cells > 0·25 × 109/l of 7·7 months whereas it was 2·8 months in UBMT (P < 0·001). B cell recovery was better in UCBT, with a median time to reach CD19+ cells > 0·2 × 109/l of 3·2 months in UCBT and 6·4 months in UBMT (P = 0·03). Median time for CD4+ T cell and NK cell recovery was similar in UCBT and UBMT. CD4+ T cells recovery was negatively correlated to age (better reconstitution in younger patients, P = 0·002). CD8+ T cells recovery was shorter in recipients with a positive cytomegalovirus serology (P = 0·001). 相似文献
999.
Meziri F Binda D Touati S Pellegrin M Berthelot A Touyz RM Laurant P 《European journal of applied physiology》2011,111(8):1929-1938
Chronic administration of recombinant human erythropoietin (rHuEPO) can generate serious cardiovascular side effects such
as arterial hypertension (HTA) in clinical and sport fields. It is hypothesized that nitric oxide (NO) can protect from noxious
cardiovascular effects induced by chronic administration of rHuEPO. On this base, we studied the cardiovascular effects of
chronic administration of rHuEPO in exercise-trained rats treated with an inhibitor of NO synthesis (L-NAME). Rats were treated
or not with rHuEPO and/or L-NAME during 6 weeks. During the same period, rats were subjected to treadmill exercise. The blood
pressure was measured weekly. Endothelial function of isolated aorta and small mesenteric arteries were studied and the morphology
of the latter was investigated. L-NAME induced hypertension (197 ± 6 mmHg, at the end of the protocol). Exercise prevented
the rise in blood pressure induced by L-NAME (170 ± 5 mmHg). However, exercise-trained rats treated with both rHuEPO and L-NAME
developed severe hypertension (228 ± 9 mmHg). Furthermore, in these exercise-trained rats treated with rHuEPO/L-NAME, the
acetylcholine-induced relaxation was markedly impaired in isolated aorta (60% of maximal relaxation) and small mesenteric
arteries (53%). L-NAME hypertension induced an internal remodeling of small mesenteric arteries that was not modified by exercise,
rHuEPO or both. Vascular ET-1 production was not increased in rHuEPO/L-NAME/training hypertensive rats. Furthermore, we observed
that rHuEPO/L-NAME/training hypertensive rats died during the exercise or the recovery period (mortality 51%). Our findings
suggest that the use of rHuEPO in sport, in order to improve physical performance, represents a high and fatal risk factor,
especially with pre-existing cardiovascular risk. 相似文献
1000.
Gaël Manes Maxime Hebrard Béatrice Bocquet Isabelle Meunier Delphine Coustes-Chazalette Audrey Sénéchal Anne Bolland-Augé Diana Zelenika Christian P Hamel 《BMC medical genetics》2011,12(1):54