全文获取类型
收费全文 | 3893篇 |
免费 | 268篇 |
国内免费 | 5篇 |
专业分类
耳鼻咽喉 | 36篇 |
儿科学 | 140篇 |
妇产科学 | 121篇 |
基础医学 | 434篇 |
口腔科学 | 68篇 |
临床医学 | 285篇 |
内科学 | 880篇 |
皮肤病学 | 172篇 |
神经病学 | 417篇 |
特种医学 | 81篇 |
外科学 | 513篇 |
综合类 | 24篇 |
一般理论 | 2篇 |
预防医学 | 324篇 |
眼科学 | 85篇 |
药学 | 223篇 |
中国医学 | 4篇 |
肿瘤学 | 357篇 |
出版年
2023年 | 23篇 |
2022年 | 41篇 |
2021年 | 103篇 |
2020年 | 69篇 |
2019年 | 139篇 |
2018年 | 135篇 |
2017年 | 91篇 |
2016年 | 89篇 |
2015年 | 91篇 |
2014年 | 131篇 |
2013年 | 163篇 |
2012年 | 227篇 |
2011年 | 269篇 |
2010年 | 151篇 |
2009年 | 139篇 |
2008年 | 199篇 |
2007年 | 208篇 |
2006年 | 190篇 |
2005年 | 189篇 |
2004年 | 165篇 |
2003年 | 163篇 |
2002年 | 171篇 |
2001年 | 94篇 |
2000年 | 124篇 |
1999年 | 92篇 |
1998年 | 43篇 |
1997年 | 32篇 |
1996年 | 27篇 |
1995年 | 28篇 |
1994年 | 16篇 |
1993年 | 24篇 |
1992年 | 46篇 |
1991年 | 45篇 |
1990年 | 33篇 |
1989年 | 40篇 |
1988年 | 30篇 |
1987年 | 25篇 |
1986年 | 31篇 |
1985年 | 31篇 |
1984年 | 31篇 |
1983年 | 20篇 |
1982年 | 11篇 |
1980年 | 13篇 |
1979年 | 14篇 |
1978年 | 17篇 |
1977年 | 13篇 |
1976年 | 12篇 |
1975年 | 22篇 |
1973年 | 21篇 |
1972年 | 12篇 |
排序方式: 共有4166条查询结果,搜索用时 187 毫秒
21.
A. Soriano J. Gómez L. Gómez J.R. Azanza R. Pérez F. Romero M. Pons F. Bella M. Velasco J. Mensa 《European journal of clinical microbiology & infectious diseases》2007,26(5):353-356
The aim of the study presented here was to assess the efficacy and tolerability of linezolid in the treatment of orthopedic
implant infections (OII). Eighty-five patients with an OII treated with linezolid were prospectively followed up for a minimum
of 12 months from the end of antibiotic therapy. Outcome was evaluated in relation to the duration and type of symptoms (acute
or chronic) and the retention or removal of the implant. For acute and chronic infections, the respective success rates were
100 and 92.3% when the implant was removed and 72.2 and 42.8% when it was not. The median length of linezolid treatment in
acute and chronic infections was 47 and 60 days, respectively. Thrombocytopenia was observed in four (4.7%) patients and anemia
in five (5.8%). The results suggest oral linezolid is an effective and well-tolerated alternative for treating OII. 相似文献
22.
Tsai JC de Groot L Pinon JD Iacono KT Phillips JJ Seo SH Lavi E Weiss SR 《Virology》2003,312(2):369-380
Targeted recombination was carried out to select mouse hepatitis viruses (MHVs) in a defined genetic background, containing an MHV-JHM spike gene encoding either three heptad repeat 1 (HR1) substitutions (Q1067H, Q1094H, and L1114R) or L1114R alone. The recombinant virus, which expresses spike with the three substitutions, was nonfusogenic at neutral pH. Its replication was significantly inhibited by lysosomotropic agents, and it was highly neuroattenuated in vivo. In contrast, the recombinant expressing spike with L1114R alone mediated cell-to-cell fusion at neutral pH and replicated efficiently despite the presence of lysosomotropic agents; however, it still caused only subclinical morbidity and no mortality in animals. Thus, both recombinant viruses were highly attenuated and expressed viral antigen which was restricted to the olfactory bulbs and was markedly absent from other regions of the brains at 5 days postinfection. These data demonstrate that amino acid substitutions, in particular L1114R, within HR1 of the JHM spike reduced the ability of MHV to spread in the central nervous system. Furthermore, the requirements for low pH for fusion and viral entry are not prerequisites for the highly attenuated phenotype. 相似文献
23.
J R Regueiro P Perez-Aeiego P Aparicio C Martinez P Morales A Arnaiz-Villena 《European journal of immunology》1990,20(11):2411-2416
B lymphocytes require appropriate T lymphocyte cooperation to synthesize immunoglobulins (Ig). Such interaction presumably takes place after engagement of the T cell receptor (TcR) by antigen. The present work addresses B lymphocyte function (and phenotype) in a novel type of immunodeficiency which is characterized by a TcR expression defect. In contrast to expectations, the two affected siblings that were studied displayed normal in vivo antibody responses to both endogenous and exogenous protein antigens. However, they showed impaired responses to certain polysaccharide antigens together with a selective IgG2 deficiency. These results suggest that some polysaccharide responses may be more T cell dependent than previously suspected, and support the notion that T cell dysfunctions (of this or other kind), rather than Ig gene deletions, may be the molecular basis of certain IgG2 deficiencies. To rule out a concomitant gross B cell dysfunction in these individuals, B lymphocyte phenotype and function were assayed in vitro, and found to be normal. A T cell line derived from one of the siblings displayed an abnormal TcR on the cell surface, but it showed several normal TcR-mediated functions. This suggests that the low number of peripheral T lymphocytes that have been found to express low TcR levels in these immunodeficiencies may be operational, and supplying sufficient "help" for the observed normal antibody responses to all tested protein, but not polysaccharide, antigens. 相似文献
24.
Clonal heterogeneity of HLA-B27 cellular allorecognition. Delineation of immunodominant sites 总被引:2,自引:0,他引:2
P Aparicio D Jaraquemada S Rojo J A López de Castro 《European journal of immunology》1988,18(2):203-209
The fine specificity of nine cytolytic T lymphocyte (CTL) clones obtained after stimulation of HLA-B27- responder lymphocytes with B27.1+ lymphoblastoid cell lines has been analyzed. These clones defined three different reaction patterns when tested against a panel of target cells including those expressing all known HLA-B27 subtypes: (a) specific recognition of HLA-B27.1, B27.2 and B27d, (b) selective reactivity with B27.1, B27d and HLA-B40 and (c) selective recognition of B27.1, B27.2, B27d, B27f and B40. Representative clones within each group were analyzed in detail. Differences in lytic ability of the various susceptible targets within each group were established by cold target inhibition analyses and by blocking experiments with anti-CD3 and anti-CD8 monoclonal antibodies. When correlated with the known structure of the HLA-B27 subtypes, these results demonstrate the critical relevance of amino acid changes within residues 77-81 and at position 152 in modulating allospecific CTL recognition of HLA-B27.1 and suggest that these residues could be involved in the structure of immunodominant regions of this antigen. The observed cross-reactions with HLA-B40, differing from B27.1 in 16 amino acid residues, suggest that the simultaneous occurrence of multiple amino acid changes could have mutually compensatory effects, so that a cross-reactive epitope might result from various combinations of polymorphic residues. 相似文献
25.
J M Aparicio A Wakisaka A Takada N Matsuura T Yoshiki 《The Japanese journal of human genetics》1989,34(4):269-277
Polymorphism in the genes encoding the alpha (alpha), beta (beta) and gamma (gamma) chains of the human T-cell receptors was analyzed both in population and family studies. Against twelve unrelated Japanese, several out of the 15 restriction endonucleases tested, revealed restriction fragment length polymorphism. The segregation of the polymorphic fragments were confirmed among 15 members of three families. In most of the cases paternal and/or maternal haplotypes could be assigned. By testing the polymorphic enzymes among the random healthy Japanese, the frequency of each polymorphic fragment was then determined. Although the polymorphism found in this study was similar to that reported in Caucasians, some differences were observed. Such differences are discussed. The restriction fragment length polymorphism in both population and family studies, derived from alpha, beta and gamma chains of the T-cell receptor found in this report, might be useful markers for genetic analysis of the T-cell function in relation to immunological disorders. 相似文献
26.
Sandford R; Sgotto B; Aparicio S; Brenner S; Vaudin M; Wilson RK; Chissoe S; Pepin K; Bateman A; Chothia C; Hughes J; Harris P 《Human molecular genetics》1997,6(9):1483-1489
PKD1 is the major locus of the common genetic disorder autosomal dominant
polycystic kidney disease (ADPKD). Analysis of the predicted protein
sequence of the human PKD1 gene, polycystin, shows a large molecule with a
unique arrangement of extracellular domains and multiple putative
transmembrane regions. The precise function of polycystin remains unclear
with a paucity of mutations to define key structural and functional
domains. To refine the structure of this protein we have cloned the genomic
region encoding the Fugu PKD1 gene. Fugu PKD1 spans 36 kb of genomic DNA
and has greater complexity with 54 exons compared with 46 in man.
Comparative analysis of the predicted protein sequences shows a lower level
of homology than in similar studies with identity of 40 and 59% similarity.
However key structural motifs including leucine rich repeats (LRR), a
C-type lectin and LDL-A like domains and 16 PKD repeats are maintained. A
region of homology with the sea urchin REJ protein was also confirmed in
Fugu but found to extend over 1000 amino acids. Several highly conserved
intra- and extra- cellular regions, with no known sequence homologies, that
are likely to be of functional importance were detected. The likely
structure of the membrane associated region has been refined with
similarity to the PKD2 protein and voltage gated Ca2+ and Na+ channels
highlighted over part of this area. The overall protein structure has
therefore been clarified and this comparative analysis derived structure
will form the basis for the functional study of polycystin and its
individual domains.
相似文献
27.
J. Fortún A. López -San Román J. J. Velasco A. Sánchez-Sousa E. de Vicente J. Nuño C. Quereda R. Bárcena G. Monge A. Candela A. Honrubia A. Guerrero 《European journal of clinical microbiology & infectious diseases》1997,16(4):314-318
The cases of four liver transplant recipients who developed invasive candidiasis (2 cholangitis, 1 perihepatic abscess, 1 candidemia) due to azole-resistantCandida glabrata are reported. Three patients were receiving azolic compounds (2 itraconazole, 1 fluconazole) when the infection was diagnosed. All four patients received fluconazole as intestinal decontamination during the first three weeks post transplantation. The infections occurred two months after transplantation in all patients, and in one patientCandida infection was the direct cause of death. Infection of the biliary tree was the origin of candidiasis in three patients; the fourth patient developed neutropenic-related candidemia. Fluconazole MICs exceeded 16 g/ml in all cases; itraconazole MICs were 16, 2, 1, and 2 g/ml, respectively. The potential role ofCandida species other thanalbicans in these patients after administration of azole agents is discussed. 相似文献
28.
The purpose of the present study was to determine whether a high number of bacteria could be demonstrated in the upper small bowel during the chickenpox infection. Intestinal juice was drawn in nine malnourished children, during and two weeks after the acute period of the disease. The results of the study fail to demonstrate quantitative differences in the bacterial flora of the small bowel in both periods. Besides that, the bacterial overgrowth previously reported in malnutrition, is confirmed. 相似文献
29.
30.
Many proteins are involved in glucose control. The first step for glucose uptake is insulin receptor-binding. Stimulation of the insulin receptor results in rapid autophosphorylation and conformational changes in the beta chain and the subsequent phosphorylation of the insulin receptor substrate. This results in the docking of several SH2 domain proteins, including PI 3-kinase and other adapters. The final event is glucose transporter (GLUT) translocation to the cell surface. GLUT is in the cytosol but after insulin stimulation, several proteins are activated either in the GLUT vesicles or in the inner membrane. The role of the cytoskeleton is not well known, but it apparently participates in membrane fusion and vesicle mobilization. After glucose uptake, several hexokines metabolize the glucose to generate energy, convert the glucose in glycogen and store it. Type 2 diabetes is characterized by high glucose levels and insulin resistance. The insulin receptor is diminished on the cell surface membrane, tyrosine phosphorylation is decreased, serine and threonine phosphorylation is augmented. Apparently, the main problem with GLUT protein is in its translocation to the cell surface. At present, we know the role of many proteins involved in glucose control. However, we do not understand the significance of insulin resistance at the molecular level with type 2 diabetes. 相似文献