全文获取类型
收费全文 | 11370篇 |
免费 | 706篇 |
国内免费 | 127篇 |
专业分类
耳鼻咽喉 | 198篇 |
儿科学 | 74篇 |
妇产科学 | 135篇 |
基础医学 | 2087篇 |
口腔科学 | 325篇 |
临床医学 | 946篇 |
内科学 | 1852篇 |
皮肤病学 | 454篇 |
神经病学 | 1044篇 |
特种医学 | 640篇 |
外科学 | 1566篇 |
综合类 | 35篇 |
一般理论 | 2篇 |
预防医学 | 463篇 |
眼科学 | 278篇 |
药学 | 1237篇 |
中国医学 | 151篇 |
肿瘤学 | 716篇 |
出版年
2024年 | 7篇 |
2023年 | 77篇 |
2022年 | 292篇 |
2021年 | 475篇 |
2020年 | 200篇 |
2019年 | 304篇 |
2018年 | 358篇 |
2017年 | 276篇 |
2016年 | 389篇 |
2015年 | 502篇 |
2014年 | 650篇 |
2013年 | 729篇 |
2012年 | 1043篇 |
2011年 | 982篇 |
2010年 | 621篇 |
2009年 | 527篇 |
2008年 | 741篇 |
2007年 | 729篇 |
2006年 | 642篇 |
2005年 | 557篇 |
2004年 | 446篇 |
2003年 | 385篇 |
2002年 | 315篇 |
2001年 | 218篇 |
2000年 | 188篇 |
1999年 | 129篇 |
1998年 | 59篇 |
1997年 | 45篇 |
1996年 | 31篇 |
1995年 | 27篇 |
1994年 | 20篇 |
1993年 | 17篇 |
1992年 | 34篇 |
1991年 | 31篇 |
1990年 | 31篇 |
1989年 | 22篇 |
1988年 | 16篇 |
1987年 | 16篇 |
1986年 | 8篇 |
1985年 | 8篇 |
1984年 | 10篇 |
1983年 | 3篇 |
1982年 | 4篇 |
1981年 | 4篇 |
1979年 | 7篇 |
1978年 | 5篇 |
1977年 | 5篇 |
1976年 | 5篇 |
1969年 | 2篇 |
1968年 | 3篇 |
排序方式: 共有10000条查询结果,搜索用时 12 毫秒
31.
Malignant rhabdoid tumor is a distinct renal tumor in children. It had been regarded as a rhabdomyosarcomatoid variant of Wilms' tumor, but it is now thought as a separate entity. We report a case of malignant rhabdoid tumor of the kidney in a 26-month-old girl who presented with a left abdominal mass. Grossly, a large mass in the lower pole of the left kidney was well encapsulated and measured 4 x 4 x 3.5cm. On cross section, it was soft and yellowish white and showed multifocal necroses. The mass was mainly located in the medial medullary portion and compressed the renal pelvis laterally. Microscopically, the tumor masses were hypercellular and anaplastic without definite blastematous elements. In larger portion, the tumor cells had abundant eosinophilic cytoplasm and hyaline globules. In addition to the classic "rhabdoid" feature, alveolar, sclerosing, and lymphomatous patterns were seen. Ultrastructurally, tumor cells with abundant cytoplasm contained tangles of intermediate filament corresponding to vimentin in immunostaining. 相似文献
32.
Inhibition of interleukin-8 expression by dexamethasone in human cultured airway epithelial cells. 总被引:9,自引:0,他引:9
下载免费PDF全文
![点击此处可从《Immunology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
O J Kwon B T Au P D Collins J N Baraniuk I M Adcock K F Chung P J Barnes 《Immunology》1994,81(3):389-394
Interleukin-8 (IL-8) is a neutrophil chemotactic factor expressed in many cell types, including human airway epithelial cells (HAEC). Inhaled corticosteroids are now used increasingly early in the treatment of airway inflammation such as in asthma, and directly interact with HAEC at relatively high concentrations. We have investigated the effect of dexamethasone on IL-8 expression in primary cultured HAEC obtained from transplantation donors. Northern blot analysis was used to measure IL-8 mRNA levels in HAEC, and radioimmunoassay was used to measure IL-8 protein in culture supernatant fluids. We demonstrated that IL-8 was expressed by primary cultured HAEC and that this was enhanced by IL-1 beta and tumour necrosis factor-alpha stimulation, but not by IL-6 or lipopolysaccharide. Dexamethasone suppressed IL-8 mRNA expression and protein synthesis dose-dependently in both resting and stimulated HAEC. The half-life of IL-8 mRNA determined in the presence of actinomycin D was less than 1 hr, and dexamethasone preincubation had no effect on mRNA stability. These results support the view that HAEC may play an important role in the pathogenesis of airway inflammatory diseases, and that glucocorticosteroids may exert their anti-inflammatory effects by blocking IL-8 gene expression and generation in these cells. 相似文献
33.
One cDNA clone was purified from an adult Clonorchis sinensis cDNA library, and its deduced polypeptide sequence was found to be homologous with myosin regulatory light chain (MRLC) of invertebrates and vertebrates. Two amino-acid residues, Thr and Ser, were conserved at the phosphorylation sites that regulate the function of MRLCs. Recombinant C. sinensis MRLC (rCsMRLC) protein was produced and purified from Escherichia coli, and mouse anti-CsMRLC immune sera recognized a protein of molecular weight 24 kDa from a soluble protein preparation of C. sinensis. The CsMRLC protein was immunohistochemically localized to the muscle fibers of the subtegumental muscle layer and to the muscles of oral and ventral suckers. However, the rCsMRLC protein proved to be less useful antigen for the serodiagnosis of human clonorchiasis.The nucleotide sequence reported herein was submitted to GenBank and assigned accession number AY519356. 相似文献
34.
Two closely related ubiquitin C-terminal hydrolase isozymes function as reciprocal modulators of germ cell apoptosis in cryptorchid testis
下载免费PDF全文
![点击此处可从《The American journal of pathology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Kwon J Wang YL Setsuie R Sekiguchi S Sato Y Sakurai M Noda M Aoki S Yoshikawa Y Wada K 《The American journal of pathology》2004,165(4):1367-1374
The experimentally induced cryptorchid mouse model is useful for elucidating the in vivo molecular mechanism of germ cell apoptosis. Apoptosis, in general, is thought to be partly regulated by the ubiquitin-proteasome system. Here, we analyzed the function of two closely related members of the ubiquitin C-terminal hydrolase (UCH) family in testicular germ cell apoptosis experimentally induced by cryptorchidism. The two enzymes, UCH-L1 and UCH-L3, deubiquitinate ubiquitin-protein conjugates and control the cellular balance of ubiquitin. The testes of gracile axonal dystrophy (gad) mice, which lack UCH-L1, were resistant to cryptorchid stress-related injury and had reduced ubiquitin levels. The level of both anti-apoptotic (Bcl-2 family and XIAP) and prosurvival (pCREB and BDNF) proteins was significantly higher in gad mice after cryptorchid stress. In contrast, Uchl3 knockout mice showed profound testicular atrophy and apoptotic germ cell loss after cryptorchid injury. Ubiquitin level was not significantly different between wild-type and Uchl3 knockout mice, whereas the levels of Nedd8 and the apoptotic proteins p53, Bax, and caspase3 were elevated in Uchl3 knockout mice. These results demonstrate that UCH-L1 and UCH-L3 function differentially to regulate the cellular levels of anti-apoptotic, prosurvival, and apoptotic proteins during testicular germ cell apoptosis. 相似文献
35.
Su-Yeon Kang Kyoung-Ju Song Seok-Ryoul Jeong Jong-Hyun Kim Sun Park Kyongmin Kim Myung-Hee Kwon Ho-Joon Shin 《Clinical and Vaccine Immunology : CVI》2005,12(7):873-876
Naegleria fowleri, a free-living amoeba, exists as a virulent pathogen which causes fatal primary amoebic meningoencephalitis in experimental animals and humans. Using infected and immune mouse sera, we previously cloned an nfa1 gene from a cDNA library of N. fowleri by immunoscreening. The nfa1 gene (360 bp) produced a recombinant 13.1-kDa protein, and the Nfa1 protein showed pseudopodium-specific immunolocalization on a trophozoite of N. fowleri. In this study, the role of the Nfa1 protein as a cell contact mechanism of N. fowleri cocultured with target cells was observed by an immunofluorescence assay with an anti-Nfa1 polyclonal antibody. Using confocal microscopic findings, the Nfa1 protein was located on the pseudopodia of N. fowleri trophozoites. The Nfa1 protein in N. fowleri trophozoites cocultured with CHO target cells was also located on pseudopodia, as well as in a food cup formed as a phagocytic structure in close contact with target cells. The amount of nfa1 mRNA of N. fowleri was strongly increased 6 h after coculture. 相似文献
36.
Bong Hyo Lee Rong Jie Zhao Jin Young Moon Seong Shoon Yoon Jung-Ae Kim Heeduk An Young Kyu Kwon Meeyul Hwang Seong Hun Choi Insop Shim Bong Hyun Kim Chae Ha Yang 《Neuroscience letters》2008
In our previous study we demonstrated that acupuncture at Shenmen (HT7) points suppressed a decrease of accumbal dopamine (DA) release in ethanol-withdrawn rats. Furthermore, here we found that it inhibited behavioral withdrawal signs of ethanol. In an effort to better understand the mechanisms underlying this inhibition, the potential role of GABA receptor system in acupuncture was investigated. Male Sprague–Dawley rats were treated with 3 g/kg/day of ethanol (20%, w/v) or saline by intraperitoneal injection for 21 days. Following 48 or 72 h of ethanol withdrawal, acupuncture was applied at bilateral HT7 for 1 min. The selective GABAA antagonist bicuculline and the selective GABAB antagonist SCH 50911 were injected intraperitoneally 20 min before acupuncture, respectively. Importantly, suppressive effects of acupuncture on DA deficiency were completely abolished by SCH 50911, but not by bicuculline, whereas ameliorating effects of acupuncture on ethanol withdrawal syndrome were completely blocked either by SCH 50911 or bicuculline. These results suggest that acupuncture at specific acupoint HT7 may normalize the DA release in the mesolimbic system and attenuate withdrawal syndrome through the GABAB receptor system in ethanol-withdrawn rats. 相似文献
37.
Non-secretion of mutant proteins of the glaucoma gene myocilin in cultured trabecular meshwork cells and in aqueous humor 总被引:11,自引:0,他引:11
Jacobson N Andrews M Shepard AR Nishimura D Searby C Fingert JH Hageman G Mullins R Davidson BL Kwon YH Alward WL Stone EM Clark AF Sheffield VC 《Human molecular genetics》2001,10(2):117-125
Until recently, very little was known about the molecular mechanisms responsible for the development of glaucoma, a leading cause of blindness worldwide. Mutations in the glaucoma gene myocilin (MYOC, GLC1A) are associated with elevated intraocular pressure and the development of autosomal dominant juvenile glaucoma and a subset of adult-onset glaucoma. MYOC is expressed in the trabecular meshwork (TM), a tissue responsible for drainage of aqueous humor from the eye, and the tissue involved in elevated intraocular pressure associated with glaucoma. To better understand the role of MYOC in glaucoma pathogenesis, we examined the expression of normal and mutant myocilin in cultured ocular (TM) and non-ocular cells as well as in the aqueous humor of patients with and without MYOC glaucoma. Normal myocilin was secreted from cultured cells, but very little to no myocilin was secreted from cells expressing five different mutant forms of MYOC. In addition, no mutant myocilin was detected in the aqueous humor of patients harboring a nonsense MYOC mutation (Q368X). Co-transfection of cultured cells with normal and mutant myocilin led to suppression of normal myocilin secretion. These studies suggest that MYOC glaucoma is due either to insufficient levels of secreted myocilin or to compromised TM cell function caused by congestion of the TM secretory pathway. 相似文献
38.
Detection of reactive oxygen species (ROS) and apoptosis in human fragmented embryos 总被引:8,自引:2,他引:8
Yang HW; Hwang KJ; Kwon HC; Kim HS; Choi KW; Oh KS 《Human reproduction (Oxford, England)》1998,13(4):998-1002
In human in-vitro fertilization (IVF)-embryo transfer, the in-vitro culture
environment differs from in-vivo conditions in that the oxygen
concentration is higher, and in such conditions the mouse embryos show a
higher concentration of reactive oxygen species (ROS) in simple culture
media. ROS are believed to cause damage to cell membranes and DNA
fragmentation in somatic cells. This study was conducted to ascertain the
level of H2O2 concentration within embryos and the morphological features
of cell damage induced by H2O2. A total of 62 human oocytes and embryos (31
fragmented, 15 non-fragmented embryos, 16 unfertilized oocytes) was
obtained from the IVF-embryo transfer programme. The relative intensity of
H2O2 concentrations within embryos was measured using
2',7'-dichlorodihydrofluorescein diacetate by Quanti cell 500 fluorescence
imaging and DNA fragmentation was observed with transmission electron
microscopy and an in-situ apoptosis detection kit. The H2O2 concentrations
were significantly higher in fragmented embryos (72.21 +/- 9.62, mean +/-
SEM) compared to non-fragmented embryos (31.30 +/- 3.50, P < 0.05) and
unfertilized oocytes (30.75 +/- 2.67, P < 0.05). Apoptosis was observed
only in fragmented embryos, and was absent in non-fragmented embryos.
Electron microscopic findings confirmed apoptotic bodies and cytoplasmic
condensation in the fragmented blastomeres. We conclude that there is a
direct relationship between increased H2O2 concentration and apoptosis, and
that further studies should be undertaken to confirm these findings.
相似文献
39.
In this report, we describe the identification of a human leucocyte antigen-A*11 (HLA-A*11) nucleotide sequence variant, a new HLA-A*1120 by using sequence-based typing (SBT). The new allele was detected during routine HLA typing by high-resolution SBT. Allele A*1120 showed one nucleotide difference with A*110101 at codon 152 (GCG-->GAG) resulting in an amino acid change from alanine to glutamate. Residue 152 is located on alpha(2)-helix of HLA class I molecule and involved in peptide binding by constructing E pocket of peptide-binding groove, implying that the change of the residue 152 would affect the binding affinity of peptides to A*1120 allele. 相似文献
40.
Park SK An SJ Hwang IK Kim DW Jung JY Won MH Choi SY Kwon OS Jeong YG Kang TC 《Neuroscience research》2004,49(4):405-416
The present study was performed to determine whether the effects induced by GABA(B) receptor-acting drugs would be related with the alteration in GABA(B) receptor expression in the hippocampus using Mongolian gerbil, a genetic epilepsy model. The distribution patterns of both GABA(B) receptor 1A/B and GABA(B)receptor 2 immunoreactivities were similarly detected in the hippocampi of normal and seizure-prone gerbils. Following baclofen (GABA(B) receptor agonist) or phaclofen (GABA(B) receptor antagonist) treatment, GABA(B) receptor immunoreactivities were decreased or increased by dose-dependent manners, respectively. Vigabatrin (GABA transaminase inhibitor) or 3-mercaptopropionic acid (GAD inhibitor) treatment did not affect GABA(B) receptor expressions. These findings suggest that GABA(B) receptor expression in the gerbil hippocampus may be altered by baclofen or phaclofen treatment. 相似文献