全文获取类型
收费全文 | 1535篇 |
免费 | 73篇 |
国内免费 | 52篇 |
专业分类
耳鼻咽喉 | 3篇 |
儿科学 | 18篇 |
妇产科学 | 9篇 |
基础医学 | 294篇 |
口腔科学 | 12篇 |
临床医学 | 81篇 |
内科学 | 204篇 |
皮肤病学 | 14篇 |
神经病学 | 157篇 |
特种医学 | 83篇 |
外国民族医学 | 1篇 |
外科学 | 38篇 |
综合类 | 126篇 |
预防医学 | 82篇 |
眼科学 | 20篇 |
药学 | 352篇 |
中国医学 | 52篇 |
肿瘤学 | 114篇 |
出版年
2024年 | 2篇 |
2023年 | 7篇 |
2022年 | 20篇 |
2021年 | 27篇 |
2020年 | 26篇 |
2019年 | 50篇 |
2018年 | 46篇 |
2017年 | 29篇 |
2016年 | 31篇 |
2015年 | 29篇 |
2014年 | 108篇 |
2013年 | 119篇 |
2012年 | 144篇 |
2011年 | 154篇 |
2010年 | 124篇 |
2009年 | 117篇 |
2008年 | 128篇 |
2007年 | 69篇 |
2006年 | 82篇 |
2005年 | 47篇 |
2004年 | 51篇 |
2003年 | 52篇 |
2002年 | 31篇 |
2001年 | 5篇 |
2000年 | 7篇 |
1999年 | 9篇 |
1998年 | 15篇 |
1997年 | 16篇 |
1996年 | 7篇 |
1995年 | 9篇 |
1994年 | 2篇 |
1993年 | 7篇 |
1990年 | 5篇 |
1989年 | 4篇 |
1988年 | 3篇 |
1987年 | 2篇 |
1986年 | 3篇 |
1985年 | 13篇 |
1984年 | 9篇 |
1983年 | 10篇 |
1982年 | 3篇 |
1981年 | 8篇 |
1980年 | 6篇 |
1979年 | 5篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1975年 | 5篇 |
1973年 | 3篇 |
1972年 | 3篇 |
1971年 | 1篇 |
排序方式: 共有1660条查询结果,搜索用时 15 毫秒
11.
①目的 探讨过敏性鼻炎患儿血清中白细胞介素-18(IL-18)、白细胞介素-12(IL-12)、干扰素-γ(IFN-γ)的表达及其意义.②方法 采用酶联免疫吸附法检测42例变应性鼻炎患儿和20例健康志愿儿血清中IL-18、IL-12、IFN-γ的含量.同时对比常年性鼻炎及季节性鼻炎患儿血清中IL-18、IL-12、IFN-γ的含量.③结果 鼻炎组血清IL-18含量为(97.02±20.67)ng/L、IL-12含量为(72.64±15.77)ng/L、IFN-γ为(0.54±0.19)ng/L,均低于正常对照组,IL-18含量为(212.75±32.96)ng/L、IL-12含量为(136.55±17.88)ng/L、IFN-γ为(1.41±0.22)ng/L,其差异具有统计学意义(P<0.01);且常年性变应性鼻炎患儿血清中IL-18、IL-12、IFN-γ水平低于季节变应性鼻炎患儿,其差异亦有统计学意义(P<0.01).④结论 IL-18、IL-12、IFN-γ在变应性鼻炎患儿血清中表达降低,说明其可能参与了对变应性炎症中抗炎抗过敏作用,且3种免疫因子之间有协同作用. 相似文献
12.
Background The function of peroxisome proliferator-activated receptor γ (PPARγ) in hepatic fibrogenesis remains largely unknown. Curcumin is a natural substance extracted form Curcuma Longa Linn and has a variety of pharmacological effects. In this study, the effects of curcumin on the proliferation, activation and apoptosis of rat hepatic stellate cells (HSCs) through PPARγ signaling were investigated.
Methods HSCs were isolated from the normal Sprague Dawley rats through in situ peffusion of the liver with Pronase E and density-gradient centrifugation with Nycodenz. Cells were treated with curcumin, troglitazone, salvianolic acid B or GW9662. The effect on HSCs proliferation was determined by MTT colorimetry. Total RNA was extracted by TRizol reagent and gene levels were determined by semi-quantitative RT-PCR. Total cellular and nuclear protein were isolated and separated by 10% sodium dodecy Isulfate polyacrylamide gel electrophoresis. Protein levels were determined by Western blot. Cell apoptosis was detected by Hoechst 33258 staining. PPARγ subcellular distribution was detected by immunofluorescent staining. The activities of MMP-2 and 9 were measured by Gelatin zymograph assay.
Results Curcumin suppressed HSCs proliferation in a dose-dependent manner. As HSCs underwent gradual activation with culture prolongation the PPARγ nuclear expression level decreased. Curcumin up-regulated PPARγ expression and significantly inhibited the production of a-SMA and collagen Ⅰ. PPARγ is expressed in the cytoplasm and nucleus and is evenly distributed in HSCs, but accumulated in the nucleus of HSCs and disappeared from cytoplasm after curcumin treatment. Hoechst 33258 staining showed that curcumin induced the apoptosis of culture-activated HSCs and significantly increased pro-apoptotic Bax expression and reduced anti-apoptotic Bcl-2 expression. Cyclin D1 gene, activated NFKB p65 protein and TGFβR-Ⅰ protein expression were down-regulated significantly by curcumin. The activities of MMP-2 and MMP-9 were enhanced significantly by curcumin.
Conclusions Curcumin can inhibit the proliferation and activation of HSCs, induce the apoptosis of activated HSCs and enhance the activities of MMP-2 and MMP-9. The effects of curcumin are mediated through activating the PPARγ sianal transduction pathway and associated with PPARγ nuclear translocation/redistribution. 相似文献
13.
Human α-synuclein (α-Syn) is instrumental in maintaining homeostasis of monoamine neurotransmitters in brain, through its trafficking, and regulation of the cell surface expression and, thereby, activity of dopamine, serotonin and norepinephrine transporters. Here we have investigated whether other members of the synuclein family of proteins, γ-synuclein (γ-Syn) and β-synuclein (β-Syn) can similarly modulate the serotonin transporter (SERT). In Ltk− cells co-transfected with SERT and γ-Syn, γ-Syn reduced [3H]5-HT uptake, in a manner dependent on its expression levels. The decrease in SERT activity was via decreased Vmax of the transporter, without change in Km, compared to cells expressing only SERT. By contrast, β-Syn co-expression failed to alter SERT uptake activity, and neither the Vmax nor the Km was changed in the presence of β-Syn. γ-Syn modulation of SERT was only partial, with a maximal ∼27% decrease in SERT activity seen even at high expression levels of γ-Syn. By contrast, α-Syn attenuated SERT activity by ∼65% at identical expression levels as γ-Syn. Co-immunoprecipitation studies showed the presence of heteromeric protein:protein complexes between γ-Syn or α-Syn and SERT, while β-Syn failed to physically interact with SERT. Both α-Syn and γ-Syn colocalized with SERT in rat primary raphae nuclei neurons. These studies document a novel physiological role for γ-Syn in regulating 5-HT synaptic availability and homeostasis, and may be of relevance in depression and mood disorders, where SERT function is dysregulated. 相似文献
14.
15.
Loukia Katsouri Marcela P. Vizcaychipi Simon McArthur Ian Harrison Marc Suárez-Calvet Alberto Lleo Dafydd G. Lloyd Daqing Ma Magdalena Sastre 《Neurobiology of aging》2013
Noradrenergic deficits have been described in the hippocampus and the frontal cortex of Alzheimer's disease brains, which are secondary to locus coeruleus degeneration. Locus coeruleus is the brain stem nucleus responsible for synthesis of noradrenaline and from where all noradrenergic neurons project. In addition, it has been suggested that noradrenaline might play a role in modulating inflammatory responses in Alzheimer's disease. In this study we aimed to investigate the effect of various agonists and antagonists for adrenergic receptors on amyloid precursor protein processing. Among them, we found that prazosin, an α1-adrenoceptor antagonist, was able to reduce the generation of amyloid β in N2a cells. Treatment of transgenic APP23 mice with prazosin prevented memory deficits over time. Although prazosin did not influence amyloid plaque load, it induced astrocytic proliferation and increased the release of apolipoprotein E and anti-inflammatory cytokines. These findings suggest that chronic treatment with prazosin leads to an anti-inflammatory response with potential beneficial effects on cognitive performance. 相似文献
16.
《International reviews of immunology》2013,32(2):107-149
The critical role of major histocompatibility complex (MHC) gene products in T cell activation was appreciated and extensively studied well before the availability of monoclonal T cell populations. However, the availability of cloned T cells has dramatically enhanced the ability to characterize the nature of MHC-restricted recognition by T cells. In certain areas, the use of monoclonal T cells has allowed substantial extension of principles already established through the use of heterogeneous T cells. In other cases, studies employing T cell clones have led to findings which were inaccessible to approaches using only heterogeneous T cell populations. On balance, it should also be pointed out that a significant number of critical questions concerning the MHC-restricted T cell repertoire remain best approached by studying the development of interactions of functionally heterogeneous T cell populations. The present review will focus upon recent progress in several areas in which the use of cloned T cells has been particularly important in characterizing the nature of MHC-restricted recognition. In particular, the restriction of T cell recognition by class II MHC products (Ia) is examined in detail. 相似文献
17.
18.
19.
A decline in stem cell function is considered as a major cause of tissue atrophy, organ-system failure, cancer development and aging process. For a better understanding of the mechanism underlying age-related decline of stem cell function, characterization of aged stem cells is required. DNA damage induces epigenetic modifications that are associated with cell dysfunction. In mammals, γH2AX has been shown as DNA damage marker and an adaptor for recruiting chromatin modifying factors. In current study, utilizing a well-accepted Drosophila midgut model for stem-cell biology, we demonstrated aging- and oxidative stress-related accumulation of γH2AvD foci, analogous to mammal γH2AX, in Drosophila intestinal stem cells (ISCs), and obtained evidence that the changes in γH2AvD is closely associated with γ-ray-induced DNA damage in ISCs and age-related accumulation of 8-oxo-2'-deoxyguanosine. The significance of our study is to document the first direct evidence for the accumulation of age-related DNA-damage in ISCs, and to show γH2AvD as a useful biomarker in exploring the molecular mechanisms underlying stem cell aging in the Drosophila midgut. 相似文献
20.
H+/amino acid transporter 1 (PAT1) is the imino acid carrier: An intestinal nutrient/drug transporter in human and rat 总被引:1,自引:0,他引:1