全文获取类型
收费全文 | 20862篇 |
免费 | 1111篇 |
国内免费 | 110篇 |
专业分类
耳鼻咽喉 | 222篇 |
儿科学 | 416篇 |
妇产科学 | 459篇 |
基础医学 | 2674篇 |
口腔科学 | 577篇 |
临床医学 | 1618篇 |
内科学 | 5584篇 |
皮肤病学 | 521篇 |
神经病学 | 1857篇 |
特种医学 | 515篇 |
外科学 | 3242篇 |
综合类 | 103篇 |
现状与发展 | 1篇 |
一般理论 | 4篇 |
预防医学 | 1531篇 |
眼科学 | 396篇 |
药学 | 1037篇 |
中国医学 | 47篇 |
肿瘤学 | 1279篇 |
出版年
2023年 | 163篇 |
2022年 | 371篇 |
2021年 | 810篇 |
2020年 | 351篇 |
2019年 | 703篇 |
2018年 | 814篇 |
2017年 | 467篇 |
2016年 | 477篇 |
2015年 | 557篇 |
2014年 | 758篇 |
2013年 | 1062篇 |
2012年 | 1730篇 |
2011年 | 1640篇 |
2010年 | 949篇 |
2009年 | 883篇 |
2008年 | 1385篇 |
2007年 | 1415篇 |
2006年 | 1334篇 |
2005年 | 1306篇 |
2004年 | 1058篇 |
2003年 | 999篇 |
2002年 | 950篇 |
2001年 | 129篇 |
2000年 | 72篇 |
1999年 | 129篇 |
1998年 | 142篇 |
1997年 | 142篇 |
1996年 | 115篇 |
1995年 | 119篇 |
1994年 | 102篇 |
1993年 | 84篇 |
1992年 | 64篇 |
1991年 | 61篇 |
1990年 | 41篇 |
1989年 | 37篇 |
1988年 | 37篇 |
1987年 | 35篇 |
1986年 | 41篇 |
1985年 | 43篇 |
1984年 | 40篇 |
1983年 | 22篇 |
1982年 | 28篇 |
1981年 | 40篇 |
1980年 | 28篇 |
1979年 | 38篇 |
1978年 | 33篇 |
1977年 | 21篇 |
1976年 | 29篇 |
1975年 | 20篇 |
1974年 | 22篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
81.
82.
Mutations in VMK1, a mitogen-activated protein kinase gene, affect microsclerotia formation and pathogenicity in Verticillium dahliae 总被引:4,自引:0,他引:4
Rauyaree P Ospina-Giraldo MD Kang S Bhat RG Subbarao KV Grant SJ Dobinson KF 《Current genetics》2005,48(2):109-116
Verticillium dahliae is an important soil-borne fungal pathogen that causes vascular wilt diseases in a large variety of important crop plants.
Due to its persistence in the soil, control of Verticillium wilt relies heavily on soil fumigation. The global ban on methyl bromide, a highly effective soil fumigant, poses an urgent
need to develop alternative control measures against Verticillium wilt; and these might be more forthcoming with a better understanding of the molecular and cellular mechanisms that underpin
the pathogenicity of V. dahliae. In this study, we assessed the role in growth, development, and pathogenicity of VMK1, a gene encoding a mitogen-activated protein (MAP) kinase (hence, Verticillium
MAP Kinase 1). Disruption of VMK1 via Agrobacterium tumefaciens-mediated transformation, in two V. dahliae isolates, one from lettuce and the other from tomato, resulted in severely reduced virulence in diverse host plants, suggesting
that VMK1 is essential for pathogenicity and that the MAP kinase-mediated signaling pathway has a conserved role in fungal pathogenicity.
The vmk1 mutants also exhibited reduced conidiation and microsclerotia formation, suggesting that the gene is important for multiple
cellular processes.
P.R. and R.G.B. equally contributed to the work 相似文献
83.
García-González M Abdulkader I Boquete AV Neo XM Forteza J Cameselle-Teijeiro J 《Virchows Archiv : an international journal of pathology》2005,447(1):12-17
This study was undertaken to investigate cyclooxygenase-2 (COX-2) expression in follicular cells of the human thyroid. COX-2 expression was studied immunohistochemically in a total of 174 samples. COX-2 immunoreactivity was confined to the cell cytoplasm with the nuclei remaining unlabelled. COX-2 expression was observed in five cases (17.2%) of normal follicular cells and in one case (16.6%) of solid cell nests. Follicular carcinoma expressed COX-2 more frequently than follicular adenoma (93.4% vs 21.1%) (p0.001). A higher percentage of cases of papillary microcarcinomas up-regulated COX-2 in comparison with all papillary carcinomas (p0.05). However, we could not establish any relationships among COX-2, patients ages or lymph node metastases in papillary carcinomas. COX-2 expression was found in 12 (92.3%) poorly differentiated carcinomas and in 13 (92.8%) undifferentiated carcinomas. We found that COX-2 is not always useful as a marker of malignancy. Our results suggest that COX-2 plays a role in progression of all thyroid carcinomas, but in papillary carcinomas, seems more important only in the early stages. COX-2 expression in the undifferentiated carcinoma deserves special consideration due to its prognosis and to the fact that selective COX-2 inhibitors were found to enhance tumour response to radiation in some studies. 相似文献
84.
Sala F Mulet J Reddy KP Bernal JA Wikman P Valor LM Peters L König GM Criado M Sala S 《Neuroscience letters》2005,373(2):144-149
The effects of various Flustra foliacea metabolites on different types of human neuronal nicotinic acetylcholine receptors (nAChRs) expressed in Xenopus oocytes were investigated. Whereas most of the compounds tested had a small blocking effect, one of them, deformylflustrabromine, selectively increased the current obtained in alpha4beta2 receptors when co-applied with acetylcholine (ACh). The current increase was reversible and concentration-dependent. This potentiating effect was still present at saturating concentrations of acetylcholine, and no changes in single-channel conductance or reversal potential were observed, thus suggesting a modification in the gating of alpha4beta2 receptors. Dwell time analysis of single channel records indicates that the mechanism of action of deformylflustrabromine could be both an increase of the opening rate constant and a decrease of the closing rate constant on alpha4beta2 receptors. Thus, deformylflustrabromine may constitute an excellent starting point for the future development of related agents able to potentiate human neuronal nicotinic receptor function. 相似文献
85.
The time of appearance of the truncus arteriosus was studied in the chick embryo using an in ovo labeling technique. Three hundred embryos at stages 13–18 of Hamburger and Hamilton were selectively labeled at the distal end of the heart tube, using gelatine-india ink label; 122 of these embryos were reincubated and 111 of them reached stages 25–28. In these stages the final location of the label was determined. Only 95 of these embryos showed both a normal heart and a label located in it. The remaining embryos were discarded due to abnormal cardiac morphology or because the label was not found. Embryos labeled at stages 13–14 had label in the conus in 42.8% of the cases and in the boundary between the conus and the truncus arteriosus in 57.1% of the cases. Label placed at stages 15–16 was located in the conus in 6.1% of the cases, in the boundary between the conus and the truncus arteriosus in 44.8% of the cases, and in the truncus arteriosus in 48.9% of the cases. Finally, label placed at stages 17–18 was located in the boundary between the conus and the truncus arteriosus in 18.7% of the cases and in the truncus arteriosus in 81.2% of the cases. Our results permit us to conclude that the truncus arteriosus appears in the chick embryo as early as stages 15–16 of Hamburger and Hamilton (50–56 hours of incubation). © 1993 Wiley-Liss, Inc. 相似文献
86.
Premature senescence involving p53 and p16 is activated in response to constitutive MEK/MAPK mitogenic signaling 总被引:35,自引:2,他引:35
下载免费PDF全文
![点击此处可从《Genes & development》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Athena W. Lin Marta Barradas James C. Stone Linda van Aelst Manuel Serrano Scott W. Lowe 《Genes & development》1998,12(19):3008-3019
Oncogenic Ras transforms immortal rodent cells to a tumorigenic state, in part, by constitutively transmitting mitogenic signals through the mitogen-activated protein kinase (MAPK) cascade. In primary cells, Ras is initially mitogenic but eventually induces premature senescence involving the p53 and p16INK4a tumor suppressors. Constitutive activation of MEK (a component of the MAPK cascade) induces both p53 and p16, and is required for Ras-induced senescence of normal human fibroblasts. Furthermore, activated MEK permanently arrests primary murine fibroblasts but forces uncontrolled mitogenesis and transformation in cells lacking either p53 or INK4a. The precisely opposite response of normal and immortalized cells to constitutive activation of the MAPK cascade implies that premature senescence acts as a fail-safe mechanism to limit the transforming potential of excessive Ras mitogenic signaling. Consequently, constitutive MAPK signaling activates p53 and p16 as tumor suppressors. 相似文献
87.
Antonio López-Beltrán Alfonso S. Calañas Pilar Jimena Alberto L. Escudero Telma R. Campello Manuel Muñoz-Torres Fernando Escobar-Jiménez Rafael E. Carvia F. F. Nogales 《Virchows Archiv : an international journal of pathology》1997,431(2):149-151
Three further cases of mature benign cystic teratomas of the ovary associated with virilization are added to the three previously
reported in the literature. They were found in postmenopausal, obese, diabetic women aged 52, 61, and 67 years. The patients
presented with hirsutism and voice changes and clitoromegaly was present in one. Testosterone and androstenedione levels were
elevated but promptly regressed after removal of the tumours. Histologically, sheets of stromal luteinized cells were found
peripherally at the interface between the neoplasm and ovarian tissue. Luteinization of ovarian stroma induced by an unknown
factor related to diabetes mellitus is the origin of the virilization.
Received: 8 January 1997 / Accepted: 28 February 1997 相似文献
88.
Guzmán M Sánchez C Galve-Roperh I 《Journal of molecular medicine (Berlin, Germany)》2001,78(11):613-625
Cannabinoids, the active components of Cannabis sativa (marijuana), and their derivatives produce a wide spectrum of central and peripheral effects, some of which may have clinical application. The discovery of specific cannabinoid receptors and a family of endogenous ligands of those receptors has attracted much attention to cannabinoids in recent years. One of the most exciting and promising areas of current cannabinoid research is the ability of these compounds to control the cell survival/death decision. Thus cannabinoids may induce proliferation, growth arrest, or apoptosis in a number of cells, including neurons, lymphocytes, and various transformed neural and nonneural cells. The variation in drug effects may depend on experimental factors such as drug concentration, timing of drug delivery, and type of cell examined. Regarding the central nervous system, most of the experimental evidence indicates that cannabinoids may protect neurons from toxic insults such as glutamaergic overstimulation, ischemia and oxidative damage. In contrast, cannabinoids induce apoptosis of glioma cells in culture and regression of malignant gliomas in vivo. Breast and prostate cancer cells are also sensitive to cannabinoid-induced antiproliferation. Regarding the immune system, low doses of cannabinoids may enhance cell proliferation, whereas high doses of cannabinoids usually induce growth arrest or apoptosis. The neuroprotective effect of cannabinoids may have potential clinical relevance for the treatment of neurodegenerative disorders such as multiple sclerosis, Parkinson's disease, and ischemia/stroke, whereas their growth-inhibiting action on transformed cells might be useful for the management of malignant brain tumors. Ongoing investigation is in search for cannabinoid-based therapeutic strategies devoid of nondesired psychotropic effects. 相似文献
89.
The heteromeric amino acid transporters (HATs) are composed of a light and a heavy subunit linked by a disulfide bridge. The heavy subunits are the SLC3 members (rBAT and 4F2hc), whereas the light subunits are members of the SLC7 family of amino acid transporters. SLC3 proteins are type II membrane glycoproteins (i.e., one single transmembrane domain and the C-terminus located outside the cell) with a bulky extracellular domain that shows homology with alpha-glucosidases. rBAT heterodimerizes with b(0,+)AT (SLC7A9) constituting the amino acid transport b(0,+), the main system responsible for the apical reabsorption of cystine in kidney. The defect in this system causes cystinuria, the most common primary inherited aminoaciduria. 4F2hc subserves various amino acid transport systems by dimerization with different SLC7 proteins. The main role of SLC3 proteins is to help routing of the holotransporter to the plasma membrane. A working model for the biogenesis of HATs based on recent data on the rBAT/b(0,+)AT heterodimeric complex is presented. 4F2hc is a multifunctional protein, and in addition to its role in amino acid transport, it may be involved in other cellular functions. Studies on two SLC7 members (Asc-2 and AGT1) demonstrate heterodimerization with unknown heavy subunits. 相似文献
90.
Sobrinho-Simões M Preto A Rocha AS Castro P Máximo V Fonseca E Soares P 《Virchows Archiv : an international journal of pathology》2005,447(5):787-793
The newly discovered molecular features of well-differentiated thyroid carcinomas derived from follicular cells are reviewed,
within the frame of the 2004 WHO classification of thyroid tumours, under the following headings: “Follicular carcinoma”,
“Papillary carcinoma”, “Follicular variant of papillary carcinoma” and “Hürthle cell tumours”. A particular emphasis is put
on the meaning of PAX8–PPARγ rearrangements, RAS and BRAF mutations, and deletions and mutations of mitochondrial genes and of nuclear genes encoding for mitochondrial enzymes, for
thyroid tumorigenesis. 相似文献