全文获取类型
收费全文 | 527篇 |
免费 | 22篇 |
国内免费 | 1篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 15篇 |
妇产科学 | 9篇 |
基础医学 | 67篇 |
口腔科学 | 1篇 |
临床医学 | 29篇 |
内科学 | 86篇 |
皮肤病学 | 5篇 |
神经病学 | 45篇 |
特种医学 | 12篇 |
外国民族医学 | 3篇 |
外科学 | 41篇 |
综合类 | 3篇 |
预防医学 | 36篇 |
眼科学 | 8篇 |
药学 | 62篇 |
中国医学 | 7篇 |
肿瘤学 | 120篇 |
出版年
2022年 | 6篇 |
2021年 | 12篇 |
2020年 | 11篇 |
2019年 | 13篇 |
2018年 | 11篇 |
2017年 | 14篇 |
2016年 | 7篇 |
2015年 | 13篇 |
2014年 | 27篇 |
2013年 | 29篇 |
2012年 | 50篇 |
2011年 | 26篇 |
2010年 | 21篇 |
2009年 | 15篇 |
2008年 | 31篇 |
2007年 | 23篇 |
2006年 | 31篇 |
2005年 | 30篇 |
2004年 | 32篇 |
2003年 | 26篇 |
2002年 | 19篇 |
2001年 | 5篇 |
2000年 | 2篇 |
1999年 | 4篇 |
1998年 | 5篇 |
1997年 | 7篇 |
1996年 | 5篇 |
1995年 | 4篇 |
1994年 | 2篇 |
1991年 | 5篇 |
1990年 | 2篇 |
1989年 | 4篇 |
1988年 | 7篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1984年 | 3篇 |
1982年 | 4篇 |
1980年 | 3篇 |
1979年 | 4篇 |
1978年 | 7篇 |
1977年 | 5篇 |
1976年 | 3篇 |
1975年 | 4篇 |
1973年 | 1篇 |
1969年 | 1篇 |
1967年 | 1篇 |
1964年 | 1篇 |
1963年 | 1篇 |
1934年 | 1篇 |
1920年 | 1篇 |
排序方式: 共有550条查询结果,搜索用时 15 毫秒
541.
542.
Thangavel Samikkannu Kurapati V. K. Rao Nimisha Gandhi Shailendra K. Saxena Madhavan P. N. Nair 《Journal of neurovirology》2010,16(4):255-263
Human immunodeficiency virus type 1 (HIV-1) is commonly associated with immune dysfunctions and the suppression of antigen-presenting
cells. This results in immune alterations, which could lead to impaired neuronal functions, such as neuroAIDS. The neurotoxic
factor kynurenine (KYN), the rate-limiting enzyme indoleamine 2,3-dioxygenase (IDO), serotonin (5-HT), and serotonin transporter
(5-HTT) may play a role in tryptophan deficiency and serotogenic dysfunction in neuroAIDS. HIV-1 transactivator regulatory
protein (Tat) is known to play a major role in immune dysfunction. Previous studies suggest that HIV-1 B and C clades differentially
manifest neuronal dysfunctions in the infected host. In the present study we examine the effect of HIV-1 B and C clade—derived
Tat on IDO and 5-HTT gene and protein expressions by dendritic cells as studied by quantitative polymerase chain reaction
(qPCR) and Western blot. In addition, the intracellular IDO expression, IDO enzyme activity, and the levels of 5-HT and KYN
were also measured. Results indicate that HIV-1 clade B Tat up-regulates IDO and down-regulates 5-HTT gene and protein expressions.
Further, HIV-1 clade B Tat caused a reduction of 5-HT with simultaneous increase in KYN levels as compared to HIV-1 clade
C Tat. These studies suggest that HIV-1 clade B and C Tat proteins may play a differential role in the neuropathogenesis of
HIV-associated dementia (HAD) or HIV-associated neurocognitive disorder (HAND). 相似文献
543.
544.
545.
Fingas CD Bronk SF Werneburg NW Mott JL Guicciardi ME Cazanave SC Mertens JC Sirica AE Gores GJ 《Hepatology (Baltimore, Md.)》2011,54(6):2076-2088
Cholangiocarcinoma (CCA) cells paradoxically express the death ligand, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and, therefore, are dependent upon potent survival signals to circumvent TRAIL cytotoxicity. CCAs are also highly desmoplastic cancers with a tumor microenvironment rich in myofibroblasts (MFBs). Herein, we examine a role for MFB-derived CCA survival signals. We employed human KMCH-1, KMBC, HuCCT-1, TFK-1, and Mz-ChA-1 CCA cells, as well as human primary hepatic stellate and myofibroblastic LX-2 cells, for these studies. In vivo experiments were conducted using a syngeneic rat orthotopic CCA model. Coculturing CCA cells with myofibroblastic human primary hepatic stellate cells or LX-2 cells significantly decreased TRAIL-induced apoptosis in CCA cells, a cytoprotective effect abrogated by neutralizing platelet-derived growth factor (PDGF)-BB antiserum. Cytoprotection by PDGF-BB was dependent upon Hedgehog (Hh) signaling, because it was abolished by the smoothened (SMO; the transducer of Hh signaling) inhibitor, cyclopamine. PDGF-BB induced cyclic adenosine monophosphate-dependent protein kinase-dependent trafficking of SMO to the plasma membrane, resulting in glioma-associated oncogene (GLI)2 nuclear translocation and activation of a consensus GLI reporter gene-based luciferase assay. A genome-wide messenger RNA expression analysis identified 67 target genes to be commonly up- (50 genes) or down-regulated (17 genes) by both Sonic hedgehog and PDGF-BB in a cyclopamine-dependent manner in CCA cells. Finally, in a rodent CCA in vivo model, cyclopamine administration increased apoptosis in CCA cells, resulting in tumor suppression. Conclusions: MFB-derived PDGF-BB protects CCA cells from TRAIL cytotoxicity by a Hh-signaling-dependent process. These results have therapeutical implications for the treatment of human CCA. 相似文献
546.
Thangavel R Stolmeier D Yang X Anantharam P Zaheer A 《Neuropathology and applied neurobiology》2012,38(6):572-581
R. Thangavel, D. Stolmeier, X. Yang, P. Anantharam and A. Zaheer (2012) Neuropathology and Applied Neurobiology 38, 572–581 Expression of glia maturation factor in neuropathological lesions of Alzheimer's disease Aims: The pathology of Alzheimer's disease (AD) is characterized by the presence of amyloid plaques (APs), neurofibrillary tangles (NFTs), degenerating neurones, and an abundance of reactive astrocytes and microglia. We aim to examine the association between glia maturation factor (GMF) expression, activated astrocytes/microglia, APs and NFTs in AD‐affected brain regions. Methods: Brain sections were stained with Thioflavin‐S to study AD pathology and sequentially immunolabeled with antibodies against GMF, glial fibrillary acidic protein (marker for reactive astrocytes), and Ionized calcium binding adaptor molecule 1 (Iba‐1, marker for activated microglia) followed by visualization with avidin‐biotin peroxidase complex. Results: Our double immunofluorescence labelling with cell‐specific markers demonstrated the glial localization of GMF. The immunohistochemical data showed that APs and NFTs are associated with increased expression of GMF in reactive glia of AD brains compared with non‐AD controls. Conclusions: This is the first report that shows GMF, a mediator of central nervous system inflammation, is expressed in the brain regions affected in AD and that GMF is mainly localized in reactive astrocytes surrounding APs/NFTs. The distribution of GMF‐immunoreactive cells in and around Thioflavin‐S stained APs and NFTs suggests involvement of GMF in inflammatory responses through reactive glia and a role of GMF in AD pathology. 相似文献
547.
Taylor KI Probst A Miserez AR Monsch AU Tolnay M 《Nature clinical practice. Neurology》2008,4(4):226-232
Background A 66-year-old man presented with a 3-year history of personality changes marked by increasing apathy, social withdrawal and deficits in complex attention, and a 1-year history of progressive memory problems and difficulties in planning and carrying out complex tasks. Investigations Three neuropsychological examinations over 2 years, neurological examination, routine laboratory tests, brain MRI, single-photon emission CT scan, genetic analyses, and neuropathological examination. Diagnosis A clinical diagnosis of frontal-variant frontotemporal dementia was superseded by postmortem neuropathological evidence, which established a diagnosis of frontal-variant Alzheimer's disease. Management The patient and his spouse were referred for counseling, and the patient was referred for follow-up examinations. 相似文献
548.
CYP2C11, the most commonly expressed isoform of cytochrome P450 in male rat liver, was measured in spleen, thymus and bone marrow by quantitative real-time PCR and enhanced Western blotting. CYP2C11 concentrations in the lymphoid tissues were a fraction of that observed in liver, but like the liver, were sexually dimorphic (M>F) with mRNA and protein levels in agreement. Although the response to hypophysectomy varied according to tissue and sex, expression levels of CYP2C11 in all measured tissues remained greater in males. Further differences in CYP2C11 expression between liver and lymphoid tissue were observed following restoration of the circulating masculine growth hormone profile in hypophysectomized rats. In contrast to the liver where the renaturalized growth hormone profile elevated CYP2C11 expression in both sexes, the response was opposite in spleen and thymus with isoform concentrations declining in both sexes. Lastly, the divergent response of CYP2C11 between the liver and immune system was examined in cultured splenocytes exposed to different mitogens. In contrast to the dramatic depletion of CYP2C11 reported in proliferating hepatocytes, mitogen-stimulation resulted in a significant elevation in splenocyte CYP2C11 expression. In summary, we report for the first time that thymus, spleen and bone marrow express, albeit nominal, sex-dependent levels of CYP2C11 (M>F) whose regulation appears to be under some hormonal control, but very different from that of the hepatic isoform. 相似文献
549.
BACKGROUND: Interventions that restrict protein intake lower plasma urea concentration and may slow the progression of renal failure. The question arises whether the effect of a dietary protein restriction could be reinforced by enrichment of the diet with fermentable carbohydrate because these carbohydrates may stimulate the extra-renal route of nitrogen (N) excretion through the digestive route. METHODS: The influence of fermentable carbohydrate and moderate protein restriction on N metabolism was investigated in a rat model of renal failure with ablation of 70% of renal mass compared with control rats with intact kidneys. Animals were adapted to diets varying with respect to nondigestible fermentable carbohydrate (0% or 10% fructooligosaccharide [FOS]) and with respect to protein content (10% or 18% casein). RESULTS: Feeding FOS led to a considerable enlargement of the cecum (increase in contents, wall thickness, and blood flow). These changes resulted in a concomitant enhancement of urea N uptake into the cecum and a decrease in plasma urea concentration (-30%). The extent of urea uptake by the cecum was influenced by plasma urea level that was determined by the dietary protein level and by the renal function. Thus, compared with control rats, the rate of urea uptake by the cecum and the total N excreted by the uremic rats was greater under all nutritional conditions. It is noteworthy that, when expressed as a percentage of total N excretion, fecal N excretion nearly doubled in rats adapted to the low-protein diets containing FOS. These effects occurred in both control rats and in uremic rats, in which a 22% decrease in urinary N was recorded as a result of FOS in addition to the low-protein diet. Globally, decreasing the amount of protein in the diet and adding a fermentable carbohydrate led to a decrease in urinary N excretion of more than 65% in uremic rats. CONCLUSION: These results suggest a possible usefulness for combining fermentable carbohydrate, such as FOS, with a low-protein diet to increase N excretion through the digestive route in detriment of the renal route. This may represent an efficient preventive measure to relieve the renal function in case of renal failure. 相似文献