全文获取类型
收费全文 | 1810篇 |
免费 | 168篇 |
国内免费 | 104篇 |
专业分类
儿科学 | 7篇 |
妇产科学 | 1篇 |
基础医学 | 239篇 |
口腔科学 | 2篇 |
临床医学 | 47篇 |
内科学 | 102篇 |
神经病学 | 1300篇 |
特种医学 | 10篇 |
外科学 | 12篇 |
综合类 | 140篇 |
预防医学 | 8篇 |
眼科学 | 27篇 |
药学 | 132篇 |
中国医学 | 25篇 |
肿瘤学 | 30篇 |
出版年
2024年 | 7篇 |
2023年 | 33篇 |
2022年 | 30篇 |
2021年 | 56篇 |
2020年 | 59篇 |
2019年 | 61篇 |
2018年 | 48篇 |
2017年 | 44篇 |
2016年 | 51篇 |
2015年 | 58篇 |
2014年 | 78篇 |
2013年 | 89篇 |
2012年 | 69篇 |
2011年 | 92篇 |
2010年 | 107篇 |
2009年 | 88篇 |
2008年 | 95篇 |
2007年 | 84篇 |
2006年 | 96篇 |
2005年 | 81篇 |
2004年 | 75篇 |
2003年 | 55篇 |
2002年 | 74篇 |
2001年 | 58篇 |
2000年 | 24篇 |
1999年 | 39篇 |
1998年 | 46篇 |
1997年 | 50篇 |
1996年 | 40篇 |
1995年 | 45篇 |
1994年 | 29篇 |
1993年 | 25篇 |
1992年 | 27篇 |
1991年 | 26篇 |
1990年 | 25篇 |
1989年 | 18篇 |
1988年 | 13篇 |
1987年 | 6篇 |
1986年 | 8篇 |
1985年 | 14篇 |
1984年 | 12篇 |
1983年 | 19篇 |
1982年 | 10篇 |
1981年 | 7篇 |
1980年 | 7篇 |
1979年 | 3篇 |
1978年 | 1篇 |
排序方式: 共有2082条查询结果,搜索用时 0 毫秒
1.
Changes in glial fibrillary acidic protein mRNA expression after corticospinal axotomy in the adult hamster 总被引:1,自引:0,他引:1
We examined changes in the expression of glial fibrillary acidic protein (GFAP) mRNA during Wallerian degeneration in the corticospinal system of the adult Golden hamster following axotomy. GFAP is the product of a type III intermediate filament (IF) gene that is expressed specifically in mature astrocytes. A well-studied component of a complex response termed reactive astrogliosis that occurs after various types of CNS injury is the increased production of astrocytic processes filled with GFAP-containing IFs. While increased expression of GFAP during reactive astrogliosis has been well established at the protein level, little is known about whether or not changes in GFAP mRNA levels occur after CNS injury. In the present study we used in situ hybridization methods to examine this issue. A 35S-labeled mouse GFAP cDNA probe was used for in situ hybridizations of sections of the brain stem obtained 2, 7, and 14 days after unilateral transections of the corticospinal tract in the caudal medulla. Film as well as emulsion autoradiography showed a dramatic increase in GFAP mRNA labeling associated with the degenerating corticospinal tract. GFAP mRNA levels were already dramatically increased in the injured corticospinal tract by 2 days post axotomy and remained elevated at 14 days. Interestingly, in addition to the robust increase in GFAP mRNA levels specifically associated with the degenerating tract, a diffuse increase in GFAP mRNA labeling was observed throughout the grey matter of the brain stem at 2 days post-axotomy, but not after this time. Immunoblotting and immunocytochemical experiments verified that the increased GFAP mRNA levels in the degenerating corticospinal system were accompanied by an increased expression of the protein. These results demonstrate that an increase in GFAP mRNA levels occurs during Wallerian degeneration in the CNS and suggest that increased expression of the GFAP gene is a major contributor to CNS scarring that results after direct traumatic injury. 相似文献
2.
3.
R. A. nasyrov A. V. Sakharova I. G. Lyudkovskaya 《Bulletin of experimental biology and medicine》1992,114(5):1724-1727
Research Institute of Children's Infectious Diseases, Ministry of Health of the Russian Federation, St. Petersburg. Institute of Neurology, Russian Academy of Medical Sciences, Moscow. (Presented by Academician of the Russian Academy of Medical Sciences D. S. Sarkisov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 114, No. 11, pp. 548–551, November, 1992. 相似文献
4.
Identification of a cis-acting positive regulatory element of the glial fibrillary acidic protein gene 总被引:4,自引:0,他引:4
J Sarid 《Journal of neuroscience research》1991,28(2):217-228
Developmental regulation of astrocyte-specific expression of the glial fibrillary acidic protein (GFAP) gene reflects transition of immature glioblasts to mature astrocytes. Described here is the cloning and sequencing of the 5'-flanking region of the mouse GFAP gene. It contains a glial-specific positive cis-acting regulatory element that directs preferential expression of a linked reporter gene when transfected into GFAP-positive glioblastoma cells. Sequence analysis of this region revealed the presence of a putative AP-1 binding site, implying a possible role for AP-1 factors in the astroglial-specific expression of the GFAP gene. 相似文献
5.
Rick B. Meeker 《Journal of neuroimmune pharmacology》2007,2(2):154-170
Invasion of human immunodeficiency virus (HIV) into the central and peripheral nervous system produces a wide range of neurological
symptoms, which continue to persist even with adequate therapeutic suppression of the systemic viremia. The development of
therapies designed to prevent the neurological complications of HIV require a detailed understanding of the mechanisms of
virus penetration into the nervous system, infection, and subsequent neuropathogenesis. These processes, however, are difficult
to study in humans. The identification of animal lentiviruses similar to HIV has provided useful models of HIV infection that
have greatly facilitated these efforts. This review summarizes contributions made from in vitro and in vivo studies on the infectious and pathological interactions of feline immunodeficiency virus (FIV) with the nervous system. In vivo studies on FIV have provided insights into the natural progression of CNS disease as well as the contribution of various
risk factors. In vitro studies have contributed to our understanding of immune cell trafficking, CNS infection and neuropathogenesis. Together,
these studies have made unique contributions to our understanding of (1) lentiviral interactions at the blood–cerebrospinal
fluid (CSF) barrier within the choroid plexus, (2) early FIV invasion and pathogenesis in the brain, and (3) lentiviral effects
on intracellular calcium deregulation and neuronal dysfunction. The ability to combine in vitro and in vivo studies on FIV offers enormous potential to explore neuropathogenic mechanisms and generate information necessary for the
development of effective therapeutic interventions. 相似文献
6.
The adenosine-producing ectoenzyme 5'-nucleotidase has recently been shown to undergo a marked redistribution during development of the cat visual cortex and to be involved in the remodelling of ocular dominance columns (Schoen et al., J. Comp. Neurol. , 296 , 379 – 392, 1990). Using an enzyme-cytochemical technique, we now investigate the developmental redistribution of 5'-nucleotidase activity in area 17 of kittens at the ultrastructural level. Between postnatal days 35 and 42, when 5'-nucleotidase is concentrated in layer IV, enzyme reaction product occupies the clefts of asymmetrical synapses within the neuropil. During later development (9th and 13th postnatal weeks), when 5'-nucleotidase spreads over all cortical laminae, the enzyme disappears from its synaptic localization and becomes increasingly associated with astrocytic membranes. The transient appearance of 5'-nucleotidase at synapses parallels the time-course and laminar profile of the synaptic remodelling which takes place during the critical period of visual cortex development. This suggests that synapse-bound 5'-nucleotidase activity plays a role in synaptic malleability, whereas its later association with glial profiles is likely to reflect other functions of the enzyme. 相似文献
7.
P. Schubert T. Ogata S. Ferroni A. McRae Y. Nakamura K. Rudolphi 《Journal of molecular neuroscience : MN》1996,28(1-3):185-190
In view of the increasing evidence that a pathological glial activation plays a significant role in the development of neurodegenerative
diseases, we investigated the underlying molecular signaling as a possible target for a pharmacological therapy. Here, we
are particularly focusing on the endogenous modulation of the Ca2+ and cyclic nucleotide-dependent signaling by the nucleoside adenosine and its reinforcement by the xanthine derivative propentofylline
(PPF). As an experimental model, we used cultured rat microglial cells and astrocytes that are immature, show a high proliferation
rate, and resemble in several aspects pathologically activated glial cells. A prolonged increase of the cellular cAMP level
favored the differentiation of cultured astrocytes and associated properties required for the physiological nerve cell function.
On the other hand, a strengthening of the cyclic nucleotide-dependent signaling inhibited potentially neurotoxic properties
of cultured microglial cells. Similar effects were obtained by treatment with propentofylline, which mimicked modulatory adenosine
effects and increased the intracellular level of cAMP and cGMP. Such a pharmacological glial cell conditioning, obtained by
modifying the strength and the timing of these second messengers, may provide a therapy of neurodegenerative diseases in which
a pathological activation of microglial cells and astrocytes is discussed to play a pathogenic role. 相似文献
8.
Tissue sections from the brains of normal, jimpy, and shiverer mice were immunostained by the peroxidase antiperoxidase method for carbonic anhydrase (CA) and the putative astrocytic "markers" glutamine synthetase (GS) and glial fibrillary acidic protein (GFAP). The cells in normal gray matter that immunostained with anti-CA and anti-GS were similar to one another in size and process elaboration. In the normal gray matter there were relatively few GFAP-positive astrocytes. When present, these cells resembled the CA- and GS-positive cells; however, the GFAP appeared to be concentrated in the astroglial processes, as distinguished from the cell bodies. Glial cell processes, immunostained for CA or GS, surrounded blood vessels and unstained neurons in the normal gray matter. The glial cells in shiverer gray matter were similar to those in the normal gray matter. When stained for GS or GFAP, the glial cells in the jimpy gray matter appeared to be somewhat hypertrophied, and when the glial cells in this mutant were stained for CA, the nuclei appeared to be swollen. It was concluded that some of the CA-positive cells in the gray matter of the normal and of each mutant mouse brain could be astrocytes. The patterns of immunostaining in the white matter emphasized the different complements of glial cells in the mutants. In the normal and shiverer mouse corpus callosum, CA, in particular, was detected only in the oligodendrocytes, their processes, and myelin. However, the data concerning the jimpy mouse suggested that the few CA-positive cells in the corpus callosum of that mutant could be astrocytes. 相似文献
9.
The ApoE4 allele is the most well-studied genetic risk factor for Alzheimer’s disease, a condition that is increasing in prevalence and remains without a cure. Precision nutrition targeting metabolic pathways altered by ApoE4 provides a tool for the potential prevention of disease. However, no long-term human studies have been conducted to determine effective nutritional protocols for the prevention of Alzheimer’s disease in ApoE4 carriers. This may be because relatively little is yet known about the precise mechanisms by which the genetic variant confers an increased risk of dementia. Fortunately, recent research is beginning to shine a spotlight on these mechanisms. These new data open up the opportunity for speculation as to how carriers might ameliorate risk through lifestyle and nutrition. Herein, we review recent discoveries about how ApoE4 differentially impacts microglia and inflammatory pathways, astrocytes and lipid metabolism, pericytes and blood–brain barrier integrity, and insulin resistance and glucose metabolism. We use these data as a basis to speculate a precision nutrition approach for ApoE4 carriers, including a low-glycemic index diet with a ketogenic option, specific Mediterranean-style food choices, and a panel of seven nutritional supplements. Where possible, we integrate basic scientific mechanisms with human observational studies to create a more complete and convincing rationale for this precision nutrition approach. Until recent research discoveries can be translated into long-term human studies, a mechanism-informed practical clinical approach may be useful for clinicians and patients with ApoE4 to adopt a lifestyle and nutrition plan geared towards Alzheimer’s risk reduction. 相似文献
10.
Amoeboid Microglial Cells and not Astrocytes Synthesize TNF-alpha in Swiss Mouse Brain Cell Cultures 总被引:1,自引:0,他引:1
Hetier E Ayala J Bousseau A Denèfle P Prochiantz A 《The European journal of neuroscience》1990,2(9):762-768
The role of tumour necrosis factor (TNF-alpha) in brain physiology and pathology has been the focus of several studies. However, the source of this lymphokine in the central nervous system and the regulation of its synthesis is still poorly understood. We have therefore used purified astrocytes and brain macrophages in culture to compare the abilities of these two cell types to synthesize TNF-alpha and its mRNA. We find that, in the Swiss mouse, no significant TNF activity or TNF-alpha mRNA are produced by astrocytes, even following activation with lipopolysaccharides (LPS). On the other hand, purified microglial cells express a cytotoxic activity able to kill TNF-sensitive LM cells. Part of this activity is released into the culture medium and part remains bound to the membrane after mild paraformaldehyde treatment, demonstrating the existence in the culture of the soluble and membrane-bound forms of TNF activity. The fact that amoeboid microglial cells, and not astrocytes, are the actual source of TNF in brain cultures was further demonstrated by Northern blot analysis and in situ hybridization using a TNF-alpha specific oligonucleotide probe. The definition of the cell type which, in the CNS, is responsible for TNF synthesis will allow the regulation of this lymphokine to be analysed and opens the way for a better understanding of the interactions between amoeboid microglial cells and the other cell types which make up the nervous system. 相似文献