全文获取类型
收费全文 | 711篇 |
免费 | 32篇 |
国内免费 | 9篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 20篇 |
妇产科学 | 16篇 |
基础医学 | 133篇 |
口腔科学 | 8篇 |
临床医学 | 64篇 |
内科学 | 133篇 |
皮肤病学 | 6篇 |
神经病学 | 66篇 |
特种医学 | 71篇 |
外科学 | 52篇 |
综合类 | 4篇 |
预防医学 | 34篇 |
眼科学 | 10篇 |
药学 | 79篇 |
中国医学 | 4篇 |
肿瘤学 | 51篇 |
出版年
2023年 | 6篇 |
2022年 | 8篇 |
2021年 | 19篇 |
2020年 | 15篇 |
2019年 | 17篇 |
2018年 | 23篇 |
2017年 | 20篇 |
2016年 | 25篇 |
2015年 | 14篇 |
2014年 | 31篇 |
2013年 | 43篇 |
2012年 | 55篇 |
2011年 | 50篇 |
2010年 | 35篇 |
2009年 | 31篇 |
2008年 | 60篇 |
2007年 | 61篇 |
2006年 | 72篇 |
2005年 | 45篇 |
2004年 | 43篇 |
2003年 | 34篇 |
2002年 | 24篇 |
2001年 | 4篇 |
2000年 | 2篇 |
1999年 | 1篇 |
1998年 | 1篇 |
1997年 | 2篇 |
1995年 | 1篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1989年 | 4篇 |
1988年 | 1篇 |
1974年 | 1篇 |
1971年 | 1篇 |
排序方式: 共有752条查询结果,搜索用时 15 毫秒
1.
Thyroid-stimulating hormone restores bone volume, microarchitecture, and strength in aged ovariectomized rats. 总被引:2,自引:0,他引:2
T Kuber Sampath Petra Simic Rebecca Sendak Natasa Draca Ann E Bowe Stephen O'Brien Susan C Schiavi John M McPherson Slobodan Vukicevic 《Journal of bone and mineral research》2007,22(6):849-859
We show the systemic administration of low levels of TSH increases bone volume and improves bone microarchitecture and strength in aged OVX rats. TSH's actions are mediated by its inhibitory effects on RANKL-induced osteoclast formation and bone resorption coupled with stimulatory effects on osteoblast differentiation and bone formation, suggesting TSH directly affects bone remodeling in vivo. INTRODUCTION: Thyroid-stimulating hormone (TSH) receptor haploinsufficient mice with normal circulating thyroid hormone levels have reduced bone mass, suggesting that TSH directly affects bone remodeling. We examined whether systemic TSH administration restored bone volume in aged ovariectomized (OVX) rats and influenced osteoclast formation and osteoblast differentiation in vitro. MATERIALS AND METHODS: Sprague-Dawley rats were OVX at 6 months, and TSH therapy was started immediately after surgery (prevention mode; n = 80) or 7 mo later (restoration mode; n = 152). Hind limbs and lumbar spine BMD was measured at 2- or 4-wk intervals in vivo and ex vivo on termination at 8-16 wk. Long bones were subjected to microCT, histomorphometric, and biomechanical analyses. The direct effect of TSH was examined in osteoclast and osteoblast progenitor cultures and established rat osteosarcoma-derived osteoblastic cells. Data were analyzed by ANOVA Dunnett test. RESULTS: In the prevention mode, low doses (0.1 and 0.3 microg) of native rat TSH prevented the progressive bone loss, and importantly, did not increase serum triiodothyroxine (T3) and thyroxine (T4) levels in aged OVX rats. In restoration mode, animals receiving 0.1 and 0.3 microg TSH had increased BMD (10-11%), trabecular bone volume (100-130%), trabecular number (25-40%), trabecular thickness (45-60%), cortical thickness (5-16%), mineral apposition and bone formation rate (200-300%), and enhanced mechanical strength of the femur (51-60%) compared with control OVX rats. In vitro studies suggest that TSH's action is mediated by its inhibitory effects on RANKL-induced osteoclast formation, as shown in hematopoietic stem cells cultivated from TSH-treated OVX rats. TSH also stimulates osteoblast differentiation, as shown by effects on alkaline phosphatase activity, osteocalcin expression, and mineralization rate. CONCLUSIONS: These results show for the first time that systemically administered TSH prevents bone loss and restores bone mass in aged OVX rats through both antiresorptive and anabolic effects on bone remodeling. 相似文献
2.
Tatjana Pekmezovi? Natasa Ivanovi? Marina Svetel Dragana Nali? Tatjana Smiljkovi? Ranko Raicevi? Vladimir S Kosti? 《Movement disorders》2003,18(11):1389-1392
The aim of this cross-sectional study was to estimate the prevalence of different subtypes of idiopathic focal dystonia in the population of Belgrade (Serbia), Yugoslavia. On December 31, 2001, the crude prevalence of all studied types of dystonia (focal, segmental, and multifocal) in Belgrade was 13.6 per 100,000 population (11.8 per 100,000 for men and 15.2 per 100,000 for women). Type-specific prevalence for focal dystonia was 11.2 per 100,000. The prevalence for cervical dystonia, blepharospasm, writer's cramp and laryngeal dystonia were 5.9 per 100,000, 1.9 per 100,000, 1.9 per 100,000, and 1.1 per 100,000, respectively. 相似文献
3.
Adrenocorticotrophic hormone (ACTH) is essential for developmental maturation of numerous organ systems during the fetal period and for adaptation to environmental challenges. Immunocytochemical and stereological methods were used in the present study to examine the effects of dexamethasone (Dx) administration during pregnancy on fetal rat pituitary ACTH-producing cells. Doses of 0.5, 0.5 and 1.0 mg Dx/kg body weight/day were given to the dams on 3 consecutive days starting on day 16 of gestation. Morphometric analysis of the ACTH-producing cells of fetuses at 21 days of gestation revealed significant inhibition by 24% and 27%, respectively, of cell volume and cell number after maternal Dx administration, whereas the volume of cell nuclei and volume density of ACTH-stained cells were insignificantly decreased. Immunocytochemical analysis showed reduced numbers, sizes and immunopositivity of ACTH cells of 21-day-old fetuses from Dx-treated dams as compared with the control group. Maternal Dx treatment in the period of intense differentiation of the hypothalamo-hypophyseal-adrenal system had an inhibitory effect on fetal function and proliferative activity of ACTH-producing cells at 21 days of gestation. Thus, inhibition of activity of fetal ACTH-producing cells may lead to adrenal suppression, modified activity of the hypothalamo-pituitary-adrenal axis and reduced body weight possibly causing lasting functional abnormalities. 相似文献
4.
Simone Boehrer Daniel Nowak Natasa Kukoc-Zivojnov Simone Hochmuth Soo-Zin Kim Dieter Hoelzer Paris S Mitrou Eckhart Weidmann Kai Uwe Chow 《Pharmacological research》2005,51(4):367-374
BACKGROUND: The role of Daxx, in particular its ability to promote or hinder apoptosis, still remains controversial. In order to elucidate the functional relevance of Daxx in the extrinsic signaling of malignant lymphocytes Jurkat T-cells were stably transfected with a Daxx-expressing vector or with the respective Daxx-negative control vector. RESULTS: Assessing first the impact of Daxx expression on the rate of proliferation we demonstrate that overexpression of Daxx alone is not sufficient to alter proliferation in neoplastic lymphocytes. Nevertheless, expression of Daxx down-regulates anti-apoptotic Bcl-2 and up-regulates pro-apoptotic BID. In addition, Daxx-overexpressing Jurkat cells exhibit a decreased expression of the pro-caspase-8, -10, -9 and -3 and a concomitant increase of the inhibitors of apoptosis proteins survivin, XIAP, cIAP-1 and -2. We further demonstrate, that upon incubation with various chemotherapeutic agents these Daxx-induced molecular alterations sensitize Jurkat T-cells to the apoptosis-inducing effects of specific chemotherapeutic agents. CONCLUSIONS: We here outline the molecular changes elicited by Daxx on major components of the apoptotic cascade of malignant lymphocytes and demonstrate the capacity of Daxx to sensitize these cells to the apoptosis-inducing effect of various chemotherapeutic agents. 相似文献
5.
6.
Antiphospholipid syndrome (APS) has been defined as a clinical and laboratory entity. Laboratory criteria include the presence of anticardiolipin antibodies (aCL) and/or lupus anticoagulant (LA), collectively termed as antiphospholipid antibodies (aPL). However, there has been a rising interest in antibodies against so-called protein cofactors, particularly in beta(2)-glycoprotein I. In the early 90s, annexins were considered as target antigens for aPL, but at present the exact role of antibodies against annexins (aANX) remains puzzling. This review is concerned with annexin V or annexin A5 (ANXA5), a widespread member of the annexin family, and antibodies directed towards it. We have endeavoured to summarise essential information about the detection of anti-annexin V antibodies (aANXA5) and their clinical relevance. This review has also brought together some relevant published data concerning the structure, physiological role and therapeutic potential of ANXA5. 相似文献
7.
8.
Zuntar I Topić E Vukosavić D Vuković V Demarin V Begonja A Antoljak N Simundić AM 《Clinica chimica acta; international journal of clinical chemistry》2003,335(1-2):95-100
BACKGROUND: The aim of this study was to investigate the frequency of C677T methylenetetrahydrofolate reductase (MTHFR) mutation in healthy Croatian volunteers and in patients with atherosclerosis. METHODS: The C677T MTHFR gene mutation was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 640 subjects, residents of the Zagreb city or Zagreb surroundings. Control group (n=298) was healthy blood donors. Patients (n=342) were divided into two groups of those with coronary heart disease, CAD (n=247) and those with >60% carotid stenosis, CS (n=95). RESULTS: CC genotype was recorded in 45% of healthy volunteers and 46% of patients (46.3% with CS and 46.2% with CAD). TC genotype was found in 49% of healthy volunteers and 45% of patients (46.3% with CS and 44.9% with CAD). There was no significant difference (p>0.05) from the control group in the genotype or allele frequency either for the overall group of patients with atherosclerosis or for the patient subgroups. CONCLUSION: The preliminary study of MTHFR polymorphism in control subjects and cardiovascular disease/carotid stenosis patients revealed that in Croats there was a low frequency of TT genotype (6% in controls vs. 9% in patients) and T allele (31% for cases and controls). Additionally, our results did not show significantly higher frequency of MTHFR mutation in CAD and CS studied groups. 相似文献
9.
Stojanoski MM Nestorović N Negić N Filipović B Sosić-Jurjević B Milosević V Sekulić M 《Anatomy and embryology》2006,211(1):61-69
Elevated glucocorticoid level in the gravid female circulation affects number of endocrine functions in fetuses and offspring.
In this research female rats were injected with dexamethasone (Dx) in three consecutive daily doses of 1.0, 0.5, 0.5 mg/kg
body weight, starting from day 16 of pregnancy. The influence of this treatment on the pituitary adrenocorticotrophic (ACTH)
cells and adrenal glands of 19-day-old fetuses was examined immunocytochemically and by morphometric analysis. Moreover, the
proliferative activity of adrenocortical cells was estimated after application of the mitotic inhibitor Oncovine. Administration
of Dx to pregnant rats induced a decline of fetal ACTH cell immunopositivity and significant decreases of ACTH cell volume
(23%, p<0.05), volume density (41%, p<0.05), and its number per unit area (17%, p<0.05) in comparison to the control 19-day-old fetuses. Reduced proliferative activity of adrenocortical cells (31%; p<0.05) in zona glomerulosa, as well as the volume of this zone were detected. The volume and number of fetal adrenocortical
cells in the inner zone and chromoblasts were not significantly reduced after Dx treatment of pregnant rats. These results
show that maternal Dx administration in the period when the fetal hypothalamo-pituitary-adrenal (PA) axis begins its function
inhibited the PA axis. Reduced ACTH cell function and mitotic activity led to suppression of adrenocortical cell multiplication
in zona glomerulosa, the region of the adrenal cortex where most proliferating cells were found in control 19-day-old fetuses.
Thus, increased glucocorticoid levels during late pregnancy caused developmental modifications involving the fetal PA axis,
which could be the basis of the altered endocrine responsiveness in adult life. 相似文献
10.