全文获取类型
收费全文 | 3229篇 |
免费 | 241篇 |
国内免费 | 141篇 |
专业分类
耳鼻咽喉 | 14篇 |
儿科学 | 26篇 |
妇产科学 | 26篇 |
基础医学 | 732篇 |
口腔科学 | 289篇 |
临床医学 | 164篇 |
内科学 | 367篇 |
皮肤病学 | 29篇 |
神经病学 | 261篇 |
特种医学 | 32篇 |
外科学 | 103篇 |
综合类 | 457篇 |
现状与发展 | 1篇 |
预防医学 | 107篇 |
眼科学 | 26篇 |
药学 | 673篇 |
中国医学 | 264篇 |
肿瘤学 | 40篇 |
出版年
2024年 | 1篇 |
2023年 | 25篇 |
2022年 | 64篇 |
2021年 | 109篇 |
2020年 | 122篇 |
2019年 | 106篇 |
2018年 | 76篇 |
2017年 | 85篇 |
2016年 | 90篇 |
2015年 | 108篇 |
2014年 | 161篇 |
2013年 | 248篇 |
2012年 | 228篇 |
2011年 | 288篇 |
2010年 | 172篇 |
2009年 | 163篇 |
2008年 | 189篇 |
2007年 | 184篇 |
2006年 | 169篇 |
2005年 | 134篇 |
2004年 | 140篇 |
2003年 | 148篇 |
2002年 | 101篇 |
2001年 | 67篇 |
2000年 | 43篇 |
1999年 | 50篇 |
1998年 | 49篇 |
1997年 | 39篇 |
1996年 | 23篇 |
1995年 | 27篇 |
1994年 | 17篇 |
1993年 | 16篇 |
1992年 | 18篇 |
1991年 | 15篇 |
1990年 | 14篇 |
1989年 | 11篇 |
1988年 | 5篇 |
1987年 | 5篇 |
1986年 | 3篇 |
1985年 | 27篇 |
1984年 | 19篇 |
1983年 | 13篇 |
1982年 | 16篇 |
1981年 | 11篇 |
1980年 | 5篇 |
1979年 | 4篇 |
1978年 | 2篇 |
1976年 | 1篇 |
排序方式: 共有3611条查询结果,搜索用时 250 毫秒
81.
82.
目的 研究细菌脂多糖(lipopolysaccharide,LPS)对人根尖牙乳头干细胞(stem cells from apical palilla,SCAP)自噬的作用及影响,以探讨年轻恒牙根尖周炎损伤与修复的分子机制。方法 原代分离培养人SCAP,采用不同质量浓度(0.05、0.5、5 μg/mL)的细菌LPS处理SCAP记为LPS处理组,未加入细菌LPS的记为对照组。Western blot检测各组自噬相关基因5(autophagy related gene 5,Atg5)及自噬调节蛋白P62的表达情况,透射电子显微镜观察细菌LPS对SCAP自噬泡形态及数量的影响,数据采用SPSS18.0软件进行统计学分析。结果 原代培养的人SCAP表达间充质干细胞表面标志物CD73、CD90、CD105,不表达造血干细胞表面标记物CD45,体外诱导培养具有成骨向分化潜能。Western blot结果显示,各组间Atg5和P62的表达总的比较差异具有统计学意义(F值分别为118.227、74.144,P < 0.05)。Atg5的表达随处理组细菌LPS质量浓度的增大而升高,其中0.05 μg/mL LPS处理组Atg5相对表达量低于对照组,5 μg/mL LPS处理组Atg5相对表达量高于对照组,差异均具有统计学意义(均P < 0.05)。与对照组相比,0.5、5 μg/mL LPS处理组P62的表达降低,其中5 μg/mL LPS组P62相对表达量最低,差异均有统计学意义(均P < 0.05)。透射电子显微镜观察发现,与对照组相比,LPS处理组自噬泡数量显著增加。结论 细菌LPS能够促进人SCAP自噬的发生,提示在炎性环境下自噬可能对人SCAP生物学性能的调控发挥重要作用。 相似文献
83.
目的探究染料木素(genistein,GEN)对脂多糖(lipopolysaccharide,LPS)活化的RAW264.7细胞凋亡的影响及其可能的药理学作用机制。方法GEN预孵育RAW264.7细胞或慢病毒介导的肿瘤坏死因子α诱导蛋白8样分子2(tumor necrosis factor-α-induced protein 8-like 2,TIPE 2)过表达细胞2 h,再与LPS共孵育24 h,采用CCK 8试剂盒检测细胞活力,Annexin V-FITC/PI试剂盒检测细胞凋亡水平,qRT-PCR检测TNF-α、IL-6、caspase-8、caspase-3和TIPE 2 mRNA,Western blot检测iNOS、COX-2、caspase-8、caspase-3、TIPE 2、Akt和p-Akt蛋白表达。结果LPS促进RAW264.7细胞TNF-α、IL-6、iNOS、COX-2合成;GEN抑制LPS活化的RAW264.7细胞活力,凋亡细胞增多,并上调caspase-8、caspase-3、TIPE 2 mRNA及蛋白表达;TIPE 2过表达上调活化RAW264.7细胞caspase-8、caspase-3 mRNA及蛋白表达,减少Akt磷酸化,且与GEN具有协同作用。结论GEN可能通过上调TIPE 2抑制Akt活性,激活外源性凋亡途径,促进LPS活化的RAW264.7细胞凋亡。 相似文献
84.
85.
To assess the effect of social isolation of growing rats on 24-h rhythmicity of circulating prolactin and growth hormone (GH)
levels and submaxillary lymph node immune responses, male Wistar rats were either individually caged or kept in groups (4–5
animals per cage) for 30 d starting on d 35 of life. Plasma prolactin and GH levels, and submaxillary lymph node lymphocyte
subset populations, interferon (IFN)-γ release and mitogenic responses to concanavalin A (Con A) and lipopolysaccharide (LPS)
were determined at six time intervals during the 24 h span. Social isolation brought about changes in mean values and 24-h
pattern of plasma prolactin and GH levels and lymph node immune responses. After isolation, prolactin and GH mean values decreased,
and lymph node T, B, non T-non B, CD8+, and CD4+-CD8+ cells augmented, whereas lymph node CD4+/CD8+ ratio, IFN-γ release and mitogenic responses decreased. Social isolation resulted in disruption of 24 h rhythmicity of every
immune parameter tested. CD4+/CD8+ ratio, IFN-γ release and Concanavalin A (Con A) and lipopolysaccharide (LPS) responses correlated significantly with plasma
prolactin or GH levels while T/B ratio correlated with plasma prolactin levels only. B, non T-non B, and CD4+-CD8+ cells correlated negatively with plasma prolactin. Modifications in mean value and 24-h rhythmicity of plasma prolactin and
GH levels are presumably involved in the effect of social isolation on immune responsiveness. 相似文献
86.
目的 :探讨脂多糖 ( LPS)对培养的牛肺动脉内皮细胞 ( PAEC) 型 Na+ /H+交换器 ( NHE-1)表达的影响及其与内皮细胞死亡的关系。方法 :体外培养牛 PAEC,MTT比色检测细胞存活率 ,并提取总 RNA,应用反转录聚合酶链式反应 ( RT-PCR)及 DNA电泳技术 ,以 NHE-1与β-actin电泳条带光密度值之比 ( e/c)作数据分析 ,以其比值反映 NHE-1m RNA的表达程度。应用 Fluo3 /Amy荧光探针标记 ,激光共聚焦观察细胞内钙离子的浓度。结果 :在L PS( 0 .0 1~ 1.0 μg/ml)作用 48h后 ,MTT比色吸光度值分别为 0 .3 5± 0 .0 7,0 .3 1± 0 .0 7,0 .2 6± 0 .0 4,低于对照组 0 .44± 0 .0 6( P<0 .0 1)。e/c分别为 0 .43± 0 .11,0 .83± 0 .14 ,1.2 2± 0 .19,高于对照组 0 .2 8± 0 .0 8( P<0 .0 1,n=4)。激光共聚焦结果显示 L PS引起细胞内钙离子增多 ,呈剂量依赖型。结论 :LPS可以引起肺动脉内皮细胞NHE-1表达增加 ,抑制细胞增殖 ,导致细胞死亡 ,钙离子可能参与 NHE-1的激活及表达。 相似文献
87.
Rachmilewitz D Karmeli F Takabayashi K Hayashi T Leider-Trejo L Lee J Leoni LM Raz E 《Gastroenterology》2002,122(5):1428-1441
BACKGROUND & AIMS: Impaired mucosal barrier, cytokine imbalance, and dysregulated CD4(+) T cells play important roles in the pathogenesis of experimental colitis and human inflammatory bowel disease. Immunostimulatory DNA sequences (ISS-DNA) and their synthetic oligonucleotide analogs (ISS-ODNs) are derived from bacterial DNA, are potent activators of innate immunity at systemic and mucosal sites, and can rescue cells from death inflicted by different agents. We hypothesized that these combined effects of ISS-DNA could inhibit the damage to the colonic mucosa in chemically induced colitis and thereby limit subsequent intestinal inflammation. METHODS: The protective and the anti-inflammatory effect of ISS-ODN administration were assessed in dextran sodium sulfate-induced colitis and in 2 models of hapten-induced colitis in Balb/c mice. Similarly, these effects of ISS-ODN were assessed in spontaneous colitis occurring in IL-10 knockout mice. RESULTS: In all models of experimental and spontaneous colitis examined, ISS-ODN administration ameliorated clinical, biochemical, and histologic scores of colonic inflammation. ISS-ODN administration inhibited the induction of colonic proinflammatory cytokines and chemokines and suppressed the induction of colonic matrix metalloproteinases in both dextran sodium sulfate- and hapten-induced colitis. CONCLUSIONS: As the colon is continuously exposed to bacterial DNA, these findings suggest a physiologic, anti-inflammatory role for immunostimulatory DNA in the GI tract. Immunostimulatory DNA deserves further evaluation for the treatment of human inflammatory bowel disease. 相似文献
88.
Risa Taira Sayori Yamaguchi Kyoko Shimizu Kiminori Nakamura Tokiyoshi Ayabe Toshio Taira 《Journal of Clinical Biochemistry and Nutrition》2015,56(2):149-154
Recent studies suggest a relationship between intestinal microbiota and metabolic syndromes; however, the underlying mechanism remains unclear. To clarify this issue, we assessed the effects of bacterial cell wall components on adiponectin, leptin and resistin secretion from rat visceral adipocytes in vitro. We also measured the relative population of Firmicutes and Bacteroidetes in fecal microbiota and the amount of fecal mucin as an intestinal barrier function, when mice were fed a high-fat diet. In the present study, we demonstrated that bacterial cell wall components affect the secretion of adipokines, depending on the presence of antigens from gram-positive or gram-negative bacteria. Lipopolysaccharide markedly inhibited adiponectin, leptin, and resistin secretion, whereas peptidoglycan increased adiponectin secretion and decreased resistin secretion in vitro. In vivo experiments showed that the high-fat diet increased the population of Firmicutes and decreased that of Bacteroidetes. In contrast, the high-fat diet downregulated the stool output and fecal mucin content. These results demonstrate that bacterial cell wall components affect the onset of metabolic syndromes by mediating the secretion of adipokines from visceral adipose tissue. Furthermore, we believe that metabolic endotoxemia is not due to the increasing dominance of gram-negative bacteria, Bacteroidetes, but due to the depression of intestinal barrier function. 相似文献
89.
90.
Identification of transactivation‐responsive DNA‐binding protein 43 (TARDBP43; TDP‐43) as a novel factor for TNF‐α expression upon lipopolysaccharide stimulation in human monocytes
下载免费PDF全文
![点击此处可从《Journal of periodontal research》网站下载免费的PDF全文](/ch/ext_images/free.gif)
H. Murata T. Hattori H. Maeda S. Takashiba M. Takigawa J. Kido T. Nagata 《Journal of periodontal research》2015,50(4):452-460