全文获取类型
收费全文 | 646篇 |
免费 | 21篇 |
国内免费 | 5篇 |
专业分类
儿科学 | 22篇 |
妇产科学 | 1篇 |
基础医学 | 133篇 |
口腔科学 | 5篇 |
临床医学 | 67篇 |
内科学 | 125篇 |
皮肤病学 | 9篇 |
神经病学 | 67篇 |
特种医学 | 12篇 |
外科学 | 53篇 |
综合类 | 34篇 |
预防医学 | 31篇 |
眼科学 | 8篇 |
药学 | 62篇 |
中国医学 | 3篇 |
肿瘤学 | 40篇 |
出版年
2023年 | 3篇 |
2022年 | 20篇 |
2021年 | 17篇 |
2020年 | 54篇 |
2019年 | 18篇 |
2018年 | 31篇 |
2017年 | 13篇 |
2016年 | 17篇 |
2015年 | 19篇 |
2014年 | 21篇 |
2013年 | 10篇 |
2012年 | 67篇 |
2011年 | 21篇 |
2010年 | 33篇 |
2009年 | 24篇 |
2008年 | 12篇 |
2007年 | 3篇 |
2006年 | 3篇 |
2005年 | 7篇 |
2004年 | 9篇 |
2003年 | 10篇 |
2002年 | 14篇 |
2001年 | 11篇 |
2000年 | 7篇 |
1999年 | 7篇 |
1998年 | 14篇 |
1997年 | 19篇 |
1996年 | 20篇 |
1995年 | 19篇 |
1994年 | 16篇 |
1993年 | 12篇 |
1992年 | 6篇 |
1991年 | 5篇 |
1990年 | 7篇 |
1989年 | 5篇 |
1988年 | 3篇 |
1987年 | 9篇 |
1986年 | 6篇 |
1985年 | 11篇 |
1984年 | 8篇 |
1983年 | 7篇 |
1982年 | 3篇 |
1981年 | 7篇 |
1980年 | 13篇 |
1979年 | 5篇 |
1977年 | 4篇 |
1976年 | 4篇 |
1972年 | 2篇 |
1964年 | 2篇 |
1958年 | 2篇 |
排序方式: 共有672条查询结果,搜索用时 31 毫秒
661.
Yanjie Han Xinxin Li Fei He Jiliang Yan Chunyan Ma Xiaoli Zheng Jinli Zhang Donghui Zhang Cuiping Meng Zhen Zhang Xinying Ji 《Oncology research》2019,27(6):681-690
Plasmacytoma variability translocation 1 (PVT1), an oncogene, has been reported to be highly expressed in
many tumors, including human glioma, gastric cancer, and non-small cell lung cancer. Functionally, it could
also regulate the development of tumor cells. However, its specific roles and pathogenesis in human gliomas
are still not clear. This study investigated the function and mechanism of PVT1 knockdown in the proliferation
and malignant transformation of human gliomas. We first examined the expression levels of PVT1 and miR-
424 in human glioma tissues and cell lines. We also used gene manipulation techniques to explore the effects of
PVT1 knockdown on cell viability, migration, invasion, and miR-424. We found that PVT1 knockdown effectively inhibited cell viability, migration, and invasion of human glioma cells and increased miR-424 expression. Based on the negative correlation between PVT1 and miR-424, we then confirmed the direct interaction
between PVT1 and miR-424 using RNA immunoprecipitation (RIP) and luciferase reporter assays. Further, we
established a xenograft nude mouse model to determine the role and mechanism of PVT1 on tumor growth in
vivo. In addition, PVT1 knockdown was shown to promote miR-424 in vivo. In summary, the present study
demonstrated that PVT1 knockdown could negatively regulate miR-424 to inhibit human glioma cell activity,
migration, and invasiveness. PVT1 knockdown could negatively regulate miR-424 to inhibit cellular activity,
migration, and invasiveness in human gliomas, which explained the oncogenic mechanism of PVT1 in human
gliomas. It also suggested that PVT1 might be a novel therapeutic target for human gliomas. 相似文献
662.
Wei Wu Linyan He Yan Huang Likun Hou Wei Zhang Liping Zhang Chunyan Wu 《Oncology research》2019,27(8):879-887
An increasing number of studies have demonstrated that microRNAs (miRNAs) may play key roles in various
cancer carcinogenesis and progression, including non-small cell lung cancer (NSCLC). However, the expressions, roles, and mechanisms of miR-510 in NSCLC have, up to now, been largely undefined. In vivo assay
showed that miR-510 was upregulated in NSCLC tissues compared with that in adjacent nontumor lung tissues.
miR-510 expression was significantly correlated with TNM stage and lymph node metastasis. In vitro assay
indicated that expressions of miR-510 were also increased in NSCLC cell lines. Downregulation of miR-510
suppressed NSCLC cell proliferation and invasion in vitro. We identified SRC kinase signaling inhibitor 1
(SRCIN1) as a direct target gene of miR-510 in NSCLC. Expression of SRCIN1 was downregulated in lung
cancer cells and negatively correlated with miR-510 expression in tumor tissues. Downregulation of SRCIN1,
leading to inhibition of miR-510 expression, reversed cell proliferation and invasion in NSCLC cells. These
results showed that miR-510 acted as an oncogenic miRNA in NSCLC, partly by targeting SRCIN1, suggesting
that miR-510 can be a potential approach for the treatment of patients with malignant lung cancer. 相似文献
663.
Juxtanodin in retinal pigment epithelial cells: Expression and biological activities in regulating cell morphology and actin cytoskeleton organization
下载免费PDF全文
![点击此处可从《The Journal of comparative neurology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Fengyi Liang Ji Hyun Hwang Nicholas Weiwei Tang Walter Hunziker 《The Journal of comparative neurology》2018,526(2):205-215
Juxtanodin (JN, also known as ermin) was initially identified as an actin cytoskeleton‐related oligodendroglial protein in the rat central nervous system. It was subsequently also found in the rat olfactory neuroepithelium, especially at the apical junctional belt of the sustentacular cells. We further examined JN expression and functional roles in the retina using fluorescence histochemistry, confocal microscopy, immuno‐electron microscopy, molecular biology, and cell culture. Prominent JN expression was found in the photoreceptor‐supporting retinal pigment epithelium (RPE), especially in a zone corresponding to the apices of RPE cells, at the roots of the RPE microvilli, and at the base of RPE cells next to the Bruch's membrane. Partial co‐localization of JN immunoreactivity with F‐actin (labeled with phalloidin) was observed at the apices and bases of RPE cells. No JN was detected in other cell types of the retina. In cultured human RPE cell line ARPE‐19, expression of extrinsic JN up‐regulated formation of actin cytoskeleton stress fibers, caused redistribution of more F‐actin fibers to the cell periphery, and promoted spreading/enlargement of transfected cells. These findings suggest possible roles of JN in RPE molecular transport, phagocytosis and formation of outer blood‐retinal barrier, or possible involvement of JN expression perturbations in pathogenesis of such retinal disorders as proliferative vitreoretinopathy and age‐related macular degeneration. 相似文献
664.
目的 探讨噻托溴铵联合呼吸运动训练对早期稳定期慢性阻塞性肺疾病(COPD)患者机体免疫功能及生活质量的影响及临床意义。方法 选择2015年1月—2016年6月浙江省衢州市人民医院收治的早期稳定期COPD患者90例,按照治疗情况分为未治疗组(30例,确诊为早期稳定期COPD但拒绝治疗)、噻托溴铵组(30例,接受单纯噻托溴铵治疗)和联合治疗组(30例,接受噻托溴铵联合呼吸运动训练治疗);选取同期健康体检者30例为健康对照组。3组患者入组后均随访12个月(于入组后第1、3、6、9、12个月随访),入组时(第0个月)及每次随访时需要完成外周血淋巴细胞亚群(CD3+、CD4+、CD8+ 、CD4+/CD8+)检测、血清免疫球蛋白(IgG、IgA)检测、肺功能〔第1秒用力呼气末容积(FEV1)〕检测及慢性阻塞性肺疾病评估测试(CAT)评分,记录年急性加重次数。对随访期间相关指标的变化进行比较分析。结果 组别与时间在CD3+、CD4+、CD8+、CD4+/CD8+、IgG、IgA、FEV1、CAT评分及年急性加重次数上存在交互作用(P<0.05),组别在CD3+、CD4+、CD8+、CD4+/CD8+、IgG、IgA上主效应显著(P<0.05),时间在所有指标上主效应显著(P<0.05)。CD3+在6、9、12个月时,CD4+在1、3、6、9、12个月时,CD4+/CD8+在1、3、6、9、12个月时,IgG在6、9、12个月时,IgA在3、6、9、12个月时,联合治疗组高于未治疗组、噻托溴铵组,噻托溴铵组高于未治疗组(P<0.05)。CD8+在3、6、9、12个月时,联合治疗组低于未治疗组、噻托溴铵组,噻托溴铵组低于未治疗组(P<0.05)。3组患者CD3+、CD4+、CD8+、CD4+/CD8+、IgA、IgG与FEV1均呈正相关,与CAT评分及年急性加重次数呈负相关(P<0.05)。结论 早期稳定期COPD患者存在机体免疫功能的下降,且与肺功能及生活质量有相关性,同时此期机体免疫功能变化可反映病情。噻托溴铵联合呼吸运动训练治疗可提高早期稳定期COPD患者机体免疫功能,延缓肺功能下降速度,减少急性加重的次数;与单用噻托溴铵相比,噻托溴铵联合呼吸运动训练治疗患者获益更大。 相似文献
665.
目的 探讨感觉统合训练在高危早产儿早期干预中的应用价值,为临床早期干预提供一定依据。方法 选取2015年1月—2016年5月因脑损伤等高危因素在四川大学华西第二医院康复医学科进行干预的102例高危早产儿为研究对象。采用随机数字表法,将患儿分为对照组(50例)和观察组(52例)。两组患儿均接受神经发育疗法(NDT)训练,观察组在上述治疗方案基础上增加居家感觉统合训练内容,包括视觉训练、听力刺激、触觉训练、前庭功能训练、运动觉刺激等,总干预时间为12个月。分别在干预后3、6、12个月时,采用婴幼儿感觉功能评估量表(TSFI)评估患儿感觉发育水平,采用贝利婴幼儿发展量表(BSID)测定患儿认知发育指数(MDI)和精神运动发育指数(PDI)。结果 康复方法与时间对患儿感觉发育水平存在交互作用(P<0.001);康复方法与时间对患儿感觉发育水平主效应均显著(P=0.049、P<0.001);其中观察组在3、6、12个月时TSFI评分均高于对照组(P<0.05)。康复方法与时间对患儿MDI存在交互作用(P=0.030),康复方法与时间对患儿MDI主效应均显著(P=0.049、P<0.001)。康复方法与时间对患儿PDI无交互作用(P=0.151),康复方法与时间对患儿PDI主效应均显著(P=0.008、P<0.001)。结论 感觉统合训练能提高高危早产儿感觉能力及运动和认知功能。 相似文献
666.
目的建立胆木药材及其制剂中原儿茶酸,短小舌根草苷,3-表短小舌根草苷,异长春花苷内酰胺的测定方法。方法采用HPLC法,X-SELECT CSHTMC18色谱柱(250 mm×4.6 mm,5μm),流动相为乙腈-0.05%甲酸水,梯度洗脱;检测波长258 nm(原儿茶酸),243 nm(短小舌根草苷、3-表短小舌根草苷),226 nm(异长春花苷内酰胺);体积流量1 mL/min;柱温30℃。结果原儿茶酸、短小舌根草苷、3-表短小舌根草苷和异长春花苷内酰胺分别在0.966~154.56μg/mL、0.944~151.04μg/mL、0.954~152.64μg/mL和0.916~146.56μg/mL内具有良好的线性关系(R2≥0.999 8);4种成分在胆木药材中的平均加样回收率分别为98.2%、101.3%、97.4%和99.2%,RSD≤3.62%。在胆木注射液中的平均加样回收率为99.7%,103.0%,98.9%,100.7%,RSD≤2.44%。结论本法操作简便,结果可靠,重现性好,可作为胆木药材及其制剂质量控制的方法。 相似文献
667.
《The American journal of medicine》1985,78(6):965-970
A retrospective analysis of 10 adult patients with community-acquired Staphylococcus aureus meningitis was performed in order to elucidate the characteristics and treatment of this lethal disease. In all patients, a focus of infection outside the central nervous system was apparent at presentation. A poor prognosis was associated with severe underlying disease, greater degree of hyponatremia at presentation, development of seizures, failure of nuchal rigidity to develop, persistent or recurrent bacteremia, and the presence of concurrent S. aureus bronchopneumonia. Degree of deterioration in mental status and cerebrospinal fluid pleocytosis, protein levels, and glucose levels did not appear to have any prognostic significance. Therapy with rifampin and a semisynthetic penicillin effected a cure in all six patients treated with this regimen. In contrast, three of four patients treated with other antibiotic combinations died. On the basis of this experience, it is concluded that further trials with rifampin in combination with another anti-staphylococcal antibiotic for the treatment of S. aureus meningitis are warranted. 相似文献
668.
《Metabolic bone disease & related research》1984,5(1):17-21
The thickness of the bone walls formed at completed remodeling sites was estimated by morphometry in iliac trabecular bone from 85 normal individuals (48 women and 37 men) aged 18–90 years. The mean three-dimensional (3-D) wall thickness was 59.4 ± 5.9 μm. No sex difference was observed. The wall thickness decreased with age: Thickness (μm) = 65.56 μm. − 0.14 μm/yr × age (yr).This reduction may lead to a loss of bone with increasing age. The coefficient of variation in completed wall thickness between individuals of the same age was 7%. The factors controlling the thickness are largely unknown, but it was noted that the intraindividual distributions of linear 3-D wall thickness (proportional to the mass of the wall) were symmetric, while distributions of reciprocal 3-D thickness (proportional to the conductivity for oxygen and waste products) were markedly rightskewed. A subgroup comprising 42 individuals aged 18–56 years had been double labeled with tetracycline. The average 3-D calcification rate was 0.63 ± 0.11 μm/day. No relationship to age or sex was demonstrated. Based on the estimates of completed wall thickness and calcification rate, the mean duration of calcification at remodeling sites was calculated to be approximately 100 days. 相似文献
669.
目的 探讨血小板 (PL T)计数的参考方法。方法 以 FITC标记的 CD42 a单克隆抗体特异结合PL T膜糖蛋白 Ib- Ix(GPIb- Ix) ,用流式细胞仪术 (FCM)检测 76例全血 FITC-抗 CD42 a- GPIb/ Ix定量 PL T。用FCM测得 PL T/ RBC,乘以经准确校正的血细胞分析仪所测同一标本的 RBC值 ,得 PL T结果 (× 10 9/ L)。同时 ,将FCM所测 PL T结果与 SE- 95 0 0、NE- 15 0 0、CD- 160 0及手工法测定结果相比较。结果 FCM批内重复性高值 (5 0 1× 10 9/ L)及中值 (184× 10 9/ L)标本的变异系数 (CV) <4% ,低值 (2 3× 10 9/ L)标本 CV=11.432 % ;批间重复性 CV为 10 .792 % ,总重复性 CV<5 % ;PL T在 2 0× 10 9/ L~ 70 0× 10 9/ L 范围内线性良好 (r=0 .9975 ,P<0 .0 0 1)。测定结果在标本采集后 6小时内稳定 ,携带污染率为 0 .87%。FCM与 SE- 95 0 0、NE- 15 0 0、CD- 160 0、手工法测定 PL T结果间有良好相关性 (r>0 .975 )。结论 FCM测定 PL T- CD42 a定量 PL T特异、准确、精密 ,可望成为 PL T测定的参考方法。 相似文献
670.
《Trends in Endocrinology and Metabolism》2023,34(1):5-20
Gender differences in the functionality of the immune system have been attributed, in part, to direct and indirect effects of sex steroids, especially estrogens, on immune cell repertoire and activity. Notable are studies that have defined roles for estrogens in the regulation of the biology of dendritic cells (DCs), macrophages, T cells and natural killer (NK) cells. Although estrogens can modulate eosinophil function, the mechanisms by which this occurs and how it contributes to the pathobiology of different diseases remains underexplored. Furthermore, although the importance of eosinophils in infection is well established, it remains unclear as to how these innate immune cells, which are present in different tumors, impact the biology of cancer cells and/or response to therapeutics. The observation that eosinophilia influences the efficacy of immune checkpoint blockers (ICBs) is significant considering the role of estrogens as regulators of eosinophil function and recent studies suggesting that response to ICBs is impacted by gender. Thus, in this review, we consider what is known about the roles of estrogen(s) in regulating tissue eosinophilia/eosinophil function and how this influences the pathobiology of breast cancer (in particular). This information provides the context for a discussion of how estrogens/the estrogen receptor (ER) signaling axis can be targeted in eosinophils and how this would be expected to influence the activity of standard-of-care interventions and contemporary immunotherapy regimens in cancer(s). 相似文献