全文获取类型
收费全文 | 22396篇 |
免费 | 2164篇 |
国内免费 | 842篇 |
专业分类
耳鼻咽喉 | 84篇 |
儿科学 | 495篇 |
妇产科学 | 285篇 |
基础医学 | 4007篇 |
口腔科学 | 335篇 |
临床医学 | 1188篇 |
内科学 | 3696篇 |
皮肤病学 | 444篇 |
神经病学 | 1336篇 |
特种医学 | 546篇 |
外国民族医学 | 2篇 |
外科学 | 2444篇 |
综合类 | 2589篇 |
现状与发展 | 1篇 |
预防医学 | 1236篇 |
眼科学 | 232篇 |
药学 | 3271篇 |
2篇 | |
中国医学 | 788篇 |
肿瘤学 | 2421篇 |
出版年
2024年 | 64篇 |
2023年 | 657篇 |
2022年 | 1491篇 |
2021年 | 1347篇 |
2020年 | 1055篇 |
2019年 | 1209篇 |
2018年 | 1106篇 |
2017年 | 960篇 |
2016年 | 804篇 |
2015年 | 1007篇 |
2014年 | 1371篇 |
2013年 | 1348篇 |
2012年 | 1109篇 |
2011年 | 1290篇 |
2010年 | 1009篇 |
2009年 | 975篇 |
2008年 | 911篇 |
2007年 | 830篇 |
2006年 | 741篇 |
2005年 | 792篇 |
2004年 | 707篇 |
2003年 | 579篇 |
2002年 | 364篇 |
2001年 | 337篇 |
2000年 | 280篇 |
1999年 | 260篇 |
1998年 | 228篇 |
1997年 | 226篇 |
1996年 | 193篇 |
1995年 | 205篇 |
1994年 | 150篇 |
1993年 | 127篇 |
1992年 | 86篇 |
1991年 | 93篇 |
1990年 | 71篇 |
1989年 | 71篇 |
1988年 | 57篇 |
1987年 | 56篇 |
1986年 | 64篇 |
1985年 | 141篇 |
1984年 | 193篇 |
1983年 | 100篇 |
1982年 | 125篇 |
1981年 | 136篇 |
1980年 | 93篇 |
1979年 | 90篇 |
1978年 | 69篇 |
1977年 | 53篇 |
1976年 | 50篇 |
1975年 | 40篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
71.
72.
Mary K. Kennedy Kendall M. Mohler Kurt D. Shanebeck Peter R. Baum Kathleen S. Picha Carol A. Otten-Evans Charles A. Janeway Kenneth H. Grabstein 《European journal of immunology》1994,24(1):116-123
T cell-dependent regulation of B cell growth and differentiation involves an interaction between CD40, a B cell surface molecule, and the CD40 ligand (CD40L) which is expressed on activated CD4+ T cells. In the current study, we show that recombinant membrane-bound murine CD40L induces B cells to express costimulatory function for the proliferation of CD4+ Tcells. CD40L- or lipopolysaccharide (LPS)-activated, but not control-cultured B cells were strong costimulators of anti-CD3 or alloantigen-dependent T cell responses. The molecular interactions responsible for the increased costimulatory functions were examined by analyzing the activated B cells for changes in the expression of two costimulatory molecules, B7 and heat-stable antigen (HSA), as well as by the use of antagonists of B7 and HSA (CTLA4.Fc and 20C9, respectively). The expression of both B7 and HSA was enhanced on B cells activated with LPS. As observed in previous studies, the costimulatory activity of the LPS-activated B cells was dependent on both B7 and HSA and was completely inhibited in the presence of a combination of CTLA4.Fc and 20C9. In contrast, activation of B cells with CD40L induced the expression of B7 but did not enhance the expression of HSA. In addition the costimulatory activity of the CD40L-activated B cells was partially, but not completely, inhibited by the combination of CTLA4.Fc and 20C9. These results demonstrate that CD40L regulates costimulatory function of B cells in part by inducing the expression of B7 and suggest that CD40L-activated B cells express an additional costimulatory activity that is not associated with LPS-activated B cells. 相似文献
73.
Functionally active complement proteins C6 and C7 detected in C6- and C7-deficient individuals 总被引:4,自引:2,他引:4
R. WÜRZNER A. ORREN P. POTTER B. P. MORGAN D. PONARD P. SPTH M. BRAI M. SCHULZE L. HAPPE O. G
TZE 《Clinical and experimental immunology》1991,83(3):430-437
Two sensitive sandwich ELISAs based on monoclonal antibodies directed to native C6 and C7 allowed the detection and quantitation of these complement proteins in 20 out of 37 serum samples from individuals who had previously been classified as deficient in these proteins as assessed by immunochemical and/or functional assays. Furthermore, serum from four C6-deficient and one combined C6-/C7-deficient individual showed an increase in the terminal complement complex (TCC) and a decrease in native C6 and C7 after complement activation as assayed by specific ELISAs. Despite their (incomplete) deficiencies, these individuals therefore possess functionally active terminal complement proteins with respect to their ability to generate the TCC. As these individuals have no history of a susceptibility to neisserial infections, even low concentrations of functionally active C6 and C7 may provide sufficient protection against those micro-organisms whose destruction requires TCC formation. 相似文献
74.
ABC proteins: key molecules for lipid homeostasis 总被引:2,自引:0,他引:2
Takahashi K Kimura Y Nagata K Yamamoto A Matsuo M Ueda K 《Medical molecular morphology》2005,38(1):2-12
Forty-nine ABC protein genes exist on human chromosomes. Eukaryotic ABC proteins were originally recognized as drug efflux pumps involved in the multidrug resistance of cancer cells. However, it is now realized that one of their major physiological roles is cellular lipid transport and homeostasis, and their dysfunction is often associated with human diseases. ABCA1 and ABCA7 mediate the apolipoprotein-dependent formation of a high-density lipoprotein–cholesterol complex. ABCA3 is indispensable for pulmonary surfactant secretion. ABCG5 and ABCG8 are involved in the secretion of plant sterols and cholesterol into bile. However, the primary substrates and mechanism of action of these ABC proteins have not been precisely defined. In this review article, we first describe the general structure and functions of eukaryotic ABC proteins. The current model of ABCA1 functionality is then explained based on studies on a topological model, subcellular localization, apoA-I dependence of HDL formation, functional defects of Tangier disease mutants, and ATP hydrolysis of purified ABCA1. ABCA1 is supposed to function as a transporter of lipids as well as a receptor for apoA-I. ABCA3 is likely involved in accumulating phospholipids and cholesterol in lamellar bodies and in generating multivesicular structures. 相似文献
75.
骨形成蛋白-7对人肾小管上皮细胞株HK-2凋亡的影响 总被引:1,自引:0,他引:1
研究不同浓度的骨成形蛋白 7(BMP 7)对人近曲小管上皮细胞株HK 2凋亡的影响并初步探讨其可能的机制。应用Hoechst 332 5 8荧光染色、DNA电泳检测凋亡细胞的形态学和生化改变 ,流式细胞仪定量检测细胞的凋亡率 ,并观察凋亡特异性蛋白酶Caspase 3活性变化的情况。结果显示 ,HK 2细胞加入 1 0ng/mlTGF β处理 2 4h后 ,可明显抑制细胞生长并诱导细胞凋亡 ,呈现明显的凋亡形态学改变 ,胞核或核质内可见浓度致密的颗粒状荧光 ,DNA电泳呈现典型的“梯形条带” ,而预先加入 5 0ng/ml、 1 0 0ng/mlBMP 7共处理 2 4h后 ,可减轻TGF β对细胞的抑制作用 ,凋亡细胞亦减少 ,Caspase 3蛋白酶活性明显下降 ,细胞凋亡率下降。提示BMP 7对人肾小管上皮细胞凋亡的具有抑制作用 ,可能是通过抑制Caspase蛋白酶活性而实现的 相似文献
76.
Norrie disease caused by a gene deletion allowing carrier detection and prenatal diagnosis 总被引:10,自引:0,他引:10
Albert de La Chapelle Eeva-Marja Sankila Mikael Lindlöf Pertti Aula Reuo Norio 《Clinical genetics》1985,28(4):317-320
Carrier determination and prenatal diagnosis in Norrie disease (ND) has so far not been reported. We describe a kindred with 4 members affected by ND in which a deletion comprising gene locus DXS7 on the short arm of the X chromosome defined by probe L1.28 causes the disorder. This allowed us to predict via chorion villus biopsy that a male foetus of a carrier woman is unaffected. 相似文献
77.
Marianna Farnè Giovanna M. Tedesco Chiara Bedetti Amedea Mencarelli Daniela Rogaia Davide Colavito Giuseppe Di Cara Gabriela Stangoni Stefania Troiani Alessandra Ferlini Paolo Prontera 《American journal of medical genetics. Part A》2020,182(10):2377-2383
Mutations in the MBOAT7 gene have been described in 43 patients, belonging to 18 families, showing nonspecific clinical features (intellectual disability [ID], seizures, microcephaly or macrocephaly, and mild to moderate cerebellar atrophy) that make the clinical diagnosis difficult. Here we report the first Italian patient, a 22.5‐year‐old female, one of the oldest reported, born to apparently consanguineous parents. She shows severe ID, macrocephaly, seizures, aggressive outbursts, hyperphagia. We also documented progressive atrophy of the cerebellar vermis, that appeared not before the age of 7. The whole‐exome sequencing of the trio identified a novel homozygous variant c.1057_1058delGCinsCA (p.Ala353His) in the MBOAT7 gene. The variant is considered to be likely pathogenic, since it is absent from population database and it lies in a highly conserved amino acid residue. This disorder has a neurometabolic pathogenesis, implicating a phospholipid remodeling abnormalities. A brain hydrogen‐magnetic resonance spectroscopy (H‐MRS) examination in our patient disclosed a peculiar neurometabolic profile in the cerebellar hemispheric region. This new finding could address the clinical suspicion of MBOAT7‐related disorder, among the wide range of genetic conditions associated with ID and cerebellar atrophy. Moreover, the documented progression of cerebellar atrophy and the worsening of the disease only after some years open to the possibility of a therapeutic window after birth. 相似文献
78.
Muda M He C Martini PG Ferraro T Layfield S Taylor D Chevrier C Schweickhardt R Kelton C Ryan PL Bathgate RA 《Molecular human reproduction》2005,11(8):591-600
LGR7 and LGR8 are G protein-coupled receptors that belong to the leucine-rich repeat-containing G-protein coupled receptor (LGR) family, including the thyroid-stimulating hormone (TSH), LH and FSH receptors. LGR7 and LGR8 stimulate cAMP production upon binding of the cognate ligands, relaxin and insulin-like peptide 3 (INSL3), respectively. We cloned several novel splice variants of both LGR7 and LGR8 and analysed the function of four variants. LGR7.1 is a truncated receptor, including only the N-terminal region of the receptor and two leucine rich repeats. In contrast, LGR7.2, LGR7.10 and LGR 8.1 all contain an intact seven transmembrane domain and most of the extracellular region, lacking only one or two exons in the ectodomain. Our analysis demonstrates that although LGR7.10 and LGR8.1 are expressed at the cell surface, LGR7.2 is predominantly retained within cells and LGR7.1 is partially secreted. mRNA expression analysis revealed that several variants are co-expressed in various tissues. None of these variants were able to stimulate cAMP production following relaxin or INSL3 treatment. Unexpectedly, we did not detect any direct specific relaxin or INSL3 binding on any of the splice variants. The large number of receptor splice variants identified suggests an unforeseen complexity in the physiology of this novel hormone-receptor system. 相似文献
79.
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
80.
Hematopoiesis is regulated by a variety of signals that either originate within a developing cell or are supplied by the surrounding environment in secreted- or contact-dependent forms. This review discusses the effects of one secreted factor, interleukin-7, on the development of B lymphocytes. We describe a molecular mechanism for a crucial checkpoint during B lineage maturation, based on the integration of signals mediated by the pre-B cell receptor, the interleukin-7 receptor, and the environment in which these signals are received. 相似文献