全文获取类型
收费全文 | 804篇 |
免费 | 107篇 |
国内免费 | 24篇 |
专业分类
耳鼻咽喉 | 6篇 |
儿科学 | 4篇 |
妇产科学 | 9篇 |
基础医学 | 113篇 |
口腔科学 | 178篇 |
临床医学 | 42篇 |
内科学 | 93篇 |
皮肤病学 | 3篇 |
神经病学 | 9篇 |
特种医学 | 2篇 |
外科学 | 206篇 |
综合类 | 60篇 |
预防医学 | 20篇 |
药学 | 97篇 |
中国医学 | 39篇 |
肿瘤学 | 54篇 |
出版年
2024年 | 1篇 |
2023年 | 9篇 |
2022年 | 20篇 |
2021年 | 25篇 |
2020年 | 28篇 |
2019年 | 35篇 |
2018年 | 36篇 |
2017年 | 34篇 |
2016年 | 41篇 |
2015年 | 37篇 |
2014年 | 58篇 |
2013年 | 94篇 |
2012年 | 61篇 |
2011年 | 82篇 |
2010年 | 62篇 |
2009年 | 54篇 |
2008年 | 59篇 |
2007年 | 54篇 |
2006年 | 36篇 |
2005年 | 36篇 |
2004年 | 29篇 |
2003年 | 25篇 |
2002年 | 14篇 |
2001年 | 4篇 |
2000年 | 1篇 |
排序方式: 共有935条查询结果,搜索用时 15 毫秒
1.
Weiping Ren Bin Wu Xin Peng Jing Hua Hsiao-Nan Hao Paul H Wooley 《Journal of orthopaedic research》2006,24(8):1575-1586
Signaling of RANK (receptor activator of nuclear factor kappa B) through its ligand RANKL appears critical in osteolysis associated with aseptic loosening (AL). The purpose of this study was to investigate the role of RANK in a murine osteolysis model developed in RANK knockout (RANK(-/-)) mice. Ultra high molecular weight polyethylene (UHMWPE) debris was introduced into established air pouches on RANK(-/-) mice, followed by implantation of calvaria bone from syngeneic littermates. Wild type C57BL/6 (RANK(+/+)) mice injected with either UHMWPE or saline alone were included in this study. Pouch tissues were collected 14 days after UHMWPE inoculation for molecular and histology analysis. Results showed that UHMWPE stimulation induced strong pouch tissue inflammation in RANK(-/-) mice, as manifested by inflammatory cellular infiltration, pouch tissue proliferation, and increased gene expression of IL-1beta, TNFalpha, and RANKL. However, the UHMWPE-induced inflammation in RANK(-/-) mice was not associated with the osteoclastic bone resorption observed in RANK(+/+) mice. In RANK(+/+) mice subjected to UHMWPE stimulation, a large number of TRAP(+) cells were found on the implanted bone surface, where active osteoclastic bone resorption was observed. No TRAP(+) cells were found in UHMWPE-containing pouch tissues of RANK(-/-) mice. Consistent with the lack of osteoclastic activity shown by TRAP staining, no significant UHMWPE particle-induced bone resorption was found in RANK(-/-) mice. A well preserved bone collagen content (Van Gieson staining) and normal plateau surface contour [microcomputed tomography (microCT)] of implanted bone was observed in RANK(-/-) mice subjected to UHMWPE stimulation. In conclusion, this study provides the evidence that UHMWPE particles induce strong inflammatory responses, but not associated with osteoclastic bone resorption in RANK(-/-) mice. This indicates that RANK signaling is essential for UHMWPE particle-induced osteoclastic bone resorption, but does not participate in UHMWPE particle-induced inflammatory response. 相似文献
2.
3.
rhIGF-1对成骨细胞增殖、分化及骨保护素、骨保护素配体基因mRNA表达的影响 总被引:2,自引:1,他引:1
目的 观察不同剂量rhIGF-1对成骨细胞增殖,分化及骨保护素,骨保护素配体mRNA基因表达的影响,为明确骨保护素,骨保护素配体在骨质疏松症发病的作用机理及rhIGF-1在临床中应用提供实验依据。方法 取2代培养的大鼠成骨细胞,在rhIGF-1为0ng/ml,10ng/ml,20ng/ml,50ng/ml的浓度中培养。观察细胞的生长及钙结节的形成,MTT法,碱性磷酸酶(ALP),骨钙素(OCN)测定细胞增殖和分化,RT-PCR测定rhIGF-1对成骨细胞骨保护素,骨保护素配体基因mRNA表达的影响。结果 成骨细胞在7d可铺满瓶壁,30d可形成钙结节,rhIGF-1可促进成骨细胞的增殖,ALP和OGN的分泌,促进骨保护素,骨保护素配体基因的表达,以促进骨保护素表达明显,在rhIGF-1为10ng/ml时作用明显。结论 rhIGF-1可促进大鼠成骨细胞的增殖,分化,及骨保护素,骨保护素配体基因mRNA的表达,骨保护素mRNA表达显。rhIGF-1可能通过影响骨保护素,骨保护素配体而调节成骨细胞破骨细胞的平衡,使骨重建,从而防治骨质疏松症。 相似文献
4.
Substance P stimulates release of RANKL via COX-2 expression in human dental pulp cells 总被引:2,自引:0,他引:2
Objective: Our previous study found that substance P (SP), a sensory neuropeptide, was expressed in the dental pulp of rats during experimental
tooth movement. We examined the effects of SP on the production of prostaglandin (PG) E2 and the receptor activator of nuclear factor- B ligand (RANKL) by human dental pulp fi broblast-like (HDPF) cells.
Materials and methods: SP was added to cultured HDPF cells at concentrations ranging from of 10−4 to 10−12 mol/L. PGE2 and soluble RANKL (sRANKL) levels were determined using enzyme-linked immunosorbent assay kits. Gene expression was confi
rmed by RT-PCR analysis. Pit formation assays using dentin slices were carried out to examine the effect of SP on osteoclastogenesis.
Results: The levels of PGE2 and sRANKL increased in the presence of SP, though the increases were greater in the experimental groups in both a time-
and concentration-dependent manner, and the increase of RANKL was partially mediated by PGE2 . The gene expression of cyclooxygenase (COX)-2 and RANKL was up-regulated, and conditioned medium samples obtained from
HDPF cells treated with SP induced bone resorption.
Conclusions: SP stimulated the production of PGE2 and RANKL, and promoted bone resorption. Therefore, SP may be involved in pulpal inflammation and root resorption during
orthodontic tooth movement.
Received 11 April 2005; returned for revision 27 July 2005; returned for final revision 20 September 2005; accepted by M.
Katori 2 November 2005 相似文献
5.
目的探讨虾青素能否防治去卵巢糖尿病大鼠的骨质流失以及可能的机制。方法 3月龄雌性SD大鼠分为3组(每组6只):对照组CON(假手术),模型组OVX/T1DM(去卵巢糖尿病大鼠),药物组OVX/T1DM-ASX(去卵巢糖尿病大鼠,给予虾青素100 mg/(kg·d)。结果连续治疗60 d后,与OVX/T1DM组相比,OVX/T1DM-ASX组骨密度(BMD)明显升高(P0.01),血清I型胶原蛋白(CTX-1)、骨钙素、I型前胶原蛋白n端前肽(PINP)、抗酒石酸磷酸酶5b(TRACP 5b)水平均显著升高(P0.01)。虾青素治疗能抑制去卵巢糖尿病大鼠骨组织形态学的改变,减少骨髓脂肪细胞增加,提高OPG/RANKL的比值。结论虾青素对绝经后糖尿病骨质流失有保护作用,这种作用与调控OPG/RANKL轴有关。 相似文献
6.
乳铁蛋白对大鼠成骨细胞增殖与分化的影响 总被引:1,自引:0,他引:1
目的观察乳铁蛋白(Lf)对大鼠成骨细胞增殖分化的影响,初步探讨Lf对成骨细胞的作用机制。方法用不同浓度的Lf干预成骨细胞,在不同时间分别测定细胞数目的增殖、细胞内碱性磷酸酶活性,并用半定量RT-PCR法检测成骨细胞内RANKL/OPG mRNA基因的表达。结果Lf呈时间和浓度依赖性地促进大鼠成骨细胞增殖及碱性磷酸酶活性,每组实验在不同时间的差异均有显著的统计学意义(P<0.05),其中400μg/ml组在72h时细胞增殖数目达到最大。在碱性磷酸酶活性方面,400μg/ml组在72h时则有所下降。不同浓度Lf、不同作用时间均能促使成骨细胞中OPG mRNA表达增加,同时抑制RANKL mRNA表达。结论Lf能促进成骨细胞的增殖分化,并且能够调节成骨细胞RANKL/ OPG mRNA表达,从而抑制破骨细胞介导的骨吸收。 相似文献
7.
Evidence that genetic deletion of the TNF receptor p60 or p80 inhibits Fas mediated apoptosis in macrophages 总被引:3,自引:0,他引:3
Almost 19 members of the tumor necrosis factor (TNF) superfamily have been identified that interact with 29 different receptors. Whether these receptors communicate with each other is not understood. Recently, we have shown that receptor activator of NF-kappaB ligand signaling is modulated by genetic deletion of the TNF receptor. In the current report, we investigated the possibility of a cross-talk between Fas and TNF-alpha signaling pathway in macrophage cell lines derived from wild-type (WT) mice and from mice with genetic deletion of the type 1 TNF receptor (p60(-/-)), the type 2 TNF receptor (p80(-/-)), or both receptors (p60(-/-)p80(-/-)). We found that the macrophages expressing TNF receptors were highly sensitive to apoptosis induced by anti-Fas. The genetic deletion of TNF receptors, however, made the cells resistance to anti-Fas-induced apoptosis. Anti-Fas induced activation of caspase-3 and PARP cleavage in WT cells but not in TNF receptor-deleted cells. This difference was found to be independent of the expression of Fas, Fas-associated protein with death domain (FADD) or TNF receptor-associated death domain (TRADD). We found that anti-Fas induced recruitment of TNFR1 into Fas-complex. We also found that TRADD, which mediates TNF signaling, was constitutively bound to Fas receptor in TNF receptor-deleted cells but not in wild-type cells. Transient transfection of TNFR1 in TNFR1-deleted cells sensitized them to anti-Fas-induced apoptosis. Overall our results demonstrate that Fas signaling is modulated by the TNF receptors and thus provide the evidence of cross-talk between the receptors of two cytokines. 相似文献
8.
目的观察薯蓣皂苷片对类风湿性关节炎模型大鼠血清骨保护素(OPG)、核因子-κB受体活化因子配体(RANKL)表达水平的影响。方法 SD大鼠,随机分为6组,每组10只,其中选取10只作为正常组,其余大鼠采用弗氏完全佐剂复制类风湿性关节炎动物模型,并将造模成功的类风湿性关节炎大鼠随机分为模型组、阳性组(甲氨蝶呤组,3.8mg·kg~(-1))、薯蓣皂苷片高、中、低剂量组(10 mg·mL~(-1)、20 mg·mL~(-1)、30mg·mL~(-1)),连续灌胃给药治疗24 d后处死,采用ELISA法检测血清OPG、RANKL水平。结果薯蓣皂苷片各剂量组大鼠血清OPG、RANKL水平分别为(95.27±4.24)、(76.44±4.09)、(69.26±5.63)pmol·L~(-1)和(96.07±4.94)、(85.41±3.75)、(67.53±2.23)pmol·L~(-1),与模型组((53.92±2.83)pmol·L~(-1)和(116.18±3.02)pmol·L~(-1))相比均有显著性差异(P0.05);OPG/RANKL比值显著高于模型组。结论薯蓣皂苷片可能通过调整OPG/RANKL动态平衡而对破骨细胞功能产生影响,从而防止骨破坏。 相似文献
9.
核因子-κB(RANK)和其配体RANKL的,属于肿瘤坏死因子受体激活剂(TNF)受体配体的家庭的一员,二者结合后,破骨细胞活性增强,引起的骨吸收。而骨保护素(OPG)能与RANK竞争RANKL,抑制破骨细胞的过度表达,或者能干扰骨髓基质细胞与破骨细胞之间相互作用而诱导破骨细胞的凋亡,RANK/RANKL/OPG系统参与了不同疾病的骨吸收导致一系列溶骨性病变。骨代谢疾病中RANKL和OPG的问题,为治疗方案提供了新的靶标,正成为临床相关研究的热点之一。 相似文献
10.
目的探讨Grb2-相关蛋白2(Gab2)在核因子-κB受体活化因子配体(RANKL)诱导的乳腺癌细胞MDA-MB-213迁移中的作用。方法流式细胞术检测MDA-MB-231细胞表面RANK的表达。Transwell法测定RANKL刺激后细胞迁移能力的改变。免疫沉降及Western-blot检测RANKL刺激后p-Tyr-Gab2和Gab2的表达。结果 MDA-MB-231细胞表达RANK蛋白,RANKL诱导MDA-MB-231细胞迁移能力增强。RANKL刺激后MDA-MB-231细胞p-Tyr-Gab2表达一过性升高。结论 Gab2参与RANKL诱导的乳腺癌细胞MDA-MB-231迁移。 相似文献