全文获取类型
收费全文 | 18846篇 |
免费 | 856篇 |
国内免费 | 127篇 |
专业分类
耳鼻咽喉 | 106篇 |
儿科学 | 632篇 |
妇产科学 | 517篇 |
基础医学 | 2155篇 |
口腔科学 | 504篇 |
临床医学 | 1399篇 |
内科学 | 4980篇 |
皮肤病学 | 316篇 |
神经病学 | 1954篇 |
特种医学 | 840篇 |
外国民族医学 | 2篇 |
外科学 | 2496篇 |
综合类 | 55篇 |
一般理论 | 2篇 |
预防医学 | 851篇 |
眼科学 | 229篇 |
药学 | 1032篇 |
中国医学 | 12篇 |
肿瘤学 | 1747篇 |
出版年
2023年 | 134篇 |
2022年 | 282篇 |
2021年 | 472篇 |
2020年 | 268篇 |
2019年 | 386篇 |
2018年 | 486篇 |
2017年 | 356篇 |
2016年 | 485篇 |
2015年 | 480篇 |
2014年 | 682篇 |
2013年 | 886篇 |
2012年 | 1339篇 |
2011年 | 1342篇 |
2010年 | 785篇 |
2009年 | 703篇 |
2008年 | 1298篇 |
2007年 | 1162篇 |
2006年 | 1230篇 |
2005年 | 1129篇 |
2004年 | 1106篇 |
2003年 | 1002篇 |
2002年 | 929篇 |
2001年 | 204篇 |
2000年 | 155篇 |
1999年 | 231篇 |
1998年 | 198篇 |
1997年 | 173篇 |
1996年 | 139篇 |
1995年 | 137篇 |
1994年 | 120篇 |
1993年 | 121篇 |
1992年 | 126篇 |
1991年 | 105篇 |
1990年 | 109篇 |
1989年 | 88篇 |
1988年 | 78篇 |
1987年 | 88篇 |
1986年 | 87篇 |
1985年 | 61篇 |
1984年 | 87篇 |
1983年 | 59篇 |
1982年 | 58篇 |
1981年 | 46篇 |
1980年 | 45篇 |
1979年 | 29篇 |
1978年 | 42篇 |
1977年 | 24篇 |
1976年 | 22篇 |
1974年 | 23篇 |
1972年 | 20篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
81.
Tezak Z Prandini P Boscaro M Marin A Devaney J Marino M Fanin M Trevisan CP Park J Tyson W Finkel R Garcia C Angelini C Hoffman EP Pegoraro E 《Human mutation》2003,21(2):103-111
Complete laminin alpha2 (LAMA2) deficiency causes approximately half of congenital muscular dystrophy (CMD) cases. Many loss-of-function mutations have been reported in these severe, neonatal-onset patients, but only single missense mutations have been found in milder CMD with partial laminin alpha2 deficiency. Here, we studied nine patients diagnosed with CMD who showed abnormal white-matter signal at brain MRI and partial deficiency of laminin alpha2 on immunofluorescence of muscle biopsy. We screened the entire 9.5 kb laminin alpha2 mRNA from patient muscle biopsy by direct capillary automated sequencing, single strand conformational polymorphism (SSCP), or denaturing high performance liquid chromatography (DHPLC) of overlapping RT-PCR products followed by direct sequencing of heteroduplexes. We identified laminin alpha2 sequence changes in six of nine CMD patients. Each of the gene changes identified, except one, was novel, including three missense changes and two splice-site mutations. The finding of partial laminin alpha2 deficiency by immunostaining is not specific for laminin alpha2 gene mutation carriers, with only two patients (22%) showing clear causative mutations, and an additional three patients (33%) showing possible mutations. The clinical presentation and disease progression was homogeneous in the laminin alpha2-mutation positive and negative CMD patients. 相似文献
82.
83.
Marco Salvetti Giovanni Ristori Mauro D'Amato Carla Buttinelli Marika Falcone Cesare Fieschi Hartmut Wekerle Carlo Pozzilli 《European journal of immunology》1993,23(6):1232-1239
T lymphocytes from patients with multiple sclerosis (MS) recognize multiple myelin basic protein (MBP) epitopes. This situation complicates the design of specific immunotherapies. We investigated to which extent the T cell response to MBP is heterogeneous in single subjects in terms of preferentially recognized regions of the molecule, major histocompatibility complex (MHC) restriction, and stability over time. From each of nine patients with MS, a minimum of six MBP-specific T lymphocyte lines (TLL) were assayed for the proliferative response to a panel of overlapping peptides, encompassing the whole MBP. Predominant Tcell recognitions of distinct MBP regions were present in three patients, all HLA-DR2+, independently of the clinical features of their disease. Tcell reactivity was preferentially directed to residues 16-38 in one patient. In this case the response was also stable over time, during different phases of the disease. Predominant reactivity to residues 86-99 was detected in the two other DR2+ patients. In each of the patients with other HLA-DR haplotypes (DR2?), as well as in three DR2+ non-MS donors, the Tcell response to MBP appeared to be considerably more heterogeneous. The HLA restriction element varied among TLL recognizing the same MBP region, even when raised from the same individual. The genomic HLA typing, performed on the DRB1 and DRB5 genes in the DR2+ subjects, showed no obvious correspondence between preferential responses to regions of MBP and HLA-DR2 subtypes. In this context, a simple, new method for the genomic typing of the HLA-DRB1 gene in individuals with the HLA-DR2 serological specificity is also described. We conclude that predominant and stable T cell responses to a single MBP region can be detected in some patients with MS. In these individuals, the MHC restriction of the T cell recognition of predominant regions appears to be variable. Polymorphisms of the HLA-DR2 gene products alone do not account for the selection of the dominant MBP Tcell epitope. 相似文献
84.
The present piece of research studied the spontaneous alpha rhythm of the human brain by combining the use of a whole-cortex neuromagnetometer and Magnetic Resonance Imaging. Single trials of spontaneous brain activity were recorded from ten human subjects asked to rest, with their eyes either closed or open, in relaxed wakefulness. MEG measurements were conducted over a period of one and a half years. The replicability of the results was confirmed for eight subjects out of ten. For three subjects, the alpha rhythm did not show any reductions due to the opening of the eyes. Both field map pattern and location of the estimated source were persistently stationary during each of the bursts of oscillations of the alpha rhythm. Dipoles were concentrated in clusters, indicating the existence of several spatially distributed sources. The calcarine fissure, the parieto-occipital sulcus and the surrounding occipital and parieto-occipital areas were identified as cortical sites of the brain where the alpha rhythm may originate. For four subjects, the majority of the sources were located near or in the calcarine fissure, while for five subjects, they were located near or in the parieto-occipital sulcus and for the remaining subject they were equally divided between the two generation sites. 相似文献
85.
Most human isolates of Mycobacterium avium Mav-A and Mav-B are strong producers of hemolysin, a putative virulence factor
下载免费PDF全文
![点击此处可从《Journal of clinical microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Hemolysin was quantified in 58 isolates of Mycobacterium avium from human, animal, and environmental sources. Human Mav-A and Mav-B isolates were the strongest producers; in contrast, animal and environmental Mav-A isolates and human, animal, and environmental Mav-C organisms were low-level producers. Hemolysin production was not restricted to isolates causing invasive infections. 相似文献
86.
Role of surface-exposed loops of Haemophilus influenzae protein P2 in the mitogen-activated protein kinase cascade
下载免费PDF全文
![点击此处可从《Infection and immunity》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Galdiero S Capasso D Vitiello M D'Isanto M Pedone C Galdiero M 《Infection and immunity》2003,71(5):2798-2809
The outer membrane of gram-negative bacteria contains several proteins, and some of these proteins, the porins, have numerous biological functions in the interaction with the host; porins are involved in the activation of signal transduction pathways and, in particular, in the activation of the Raf/MEK1-MEK2/mitogen-activated protein kinase (MAPK) cascade. The P2 porin is the most abundant outer membrane protein of Haemophilus influenzae type b. A three-dimensional structural model for P2 was constructed based on the crystal structures of Klebsiella pneumoniae OmpK36 and Escherichia coli PhoE and OmpF. The protein was readily assembled into the beta-barrel fold characteristic of porins, despite the low sequence identity with the template proteins. The model provides information on the structural features of P2 and insights relevant for prediction of domains corresponding to surface-exposed loops, which could be involved in the activation of signal transduction pathways. To identify the role of surface-exposed loops, a set of synthetic peptides were synthesized according to the proposed model and were assayed for MEK1-MEK2/MAPK pathway activation. Our results show that synthetic peptides corresponding to surface loops of protein P2 are able to activate the MEK1-MEK2/MAPK pathways like the entire protein, while peptides modeled on internal beta strands are unable to induce significant phosphorylation of the MEK1-MEK2/MAPK pathways. In particular, the peptides corresponding to loops L5 (Lys206 to Gly219), L6B (Ser239 to Lys253), and L7 (Thr280 to Lys287) activate, as the whole protein, essentially JNK and p38. 相似文献
87.
Carlo Mancini Giulio Pisani Alberta Azzi Maria Luisa Zerbini Giuliano Gentili Guillermo Mario Bisso MS participants 《Journal of clinical virology》2004,30(4):313-319
BACKGROUND: The importance of the standardisation of nucleic acid amplification technology (NAT) assays for the detection of hepatitis C virus RNA is well known today, as many studies carried out in different European countries attest. The results of a previous study performed in Italy (J. Clin. Virol. 1 (2003) 83) by the Italian Society of Clinical Microbiology (AMCLI) showed that the use of external reference standards and of multicentre collaborative studies significantly improves laboratory performance for the qualitative evaluation of HCV RNA. OBJECTIVES: the AMCLI organised a new study on the standardisation of both the qualitative and the quantitative evaluation of HCV RNA with NAT in order to improve the implementation of the diagnostic methods for HCV RNA detection. STUDY DESIGN: seventeen diagnostic centres of major Italian Hospitals participated in this quality control study. The study consisted of testing three panels, each made up of 10 coded samples including negative and positive samples. Positive samples contained four levels of HCV RNA (genotype 1). RESULTS AND CONCLUSION: Seven out of 510 qualitative results obtained were incorrect (1.4%), two false negative and five false positive. The results gave a sensitivity of 99.5% and a specificity of 95.8%. Regarding quantitative tests, the geometric mean (GM) and standard deviation (S.D.) could be calculated only for the three highest HCV RNA levels. The percentage of results within the range of GM +/- 0.5 log(10) varied from 91% to 100%. Some laboratories had some difficulty in the exact quantification of the lowest (3.00 log IU/ml) as well as of the highest viral levels (6.35 log IU/ml) values, very near to the limits of the dynamic range of the assays. The comparison of the results of this study with that previously carried out one confirms that a regular participation in external quality assessment (EQA) assures the achievement of a high proficiency level in the diagnosis of HCV infection. 相似文献
88.
Parazzini Fabio; Tozzi Luca; Chatenoud Liliane; Restelli Simona; Luchini Laura; Vecchia Carlo La 《Human reproduction (Oxford, England)》1994,9(10):1950-1953
The objective of this study was to assess the association betweenalcohol drinking before and during pregnancy and the risk ofspontaneous abortion using data from a case-control study conductedin Milan, Italy. A total of 462 women (median age 30 years)were admitted for spontaneous abortion (within the 12th weekof gestation) to a network of obstetrics departments in thegreater Milan area. Of these, 148 (32%) were between the fourthand the eighth week of gestation and 314 (68%) between the ninthand the 12th week. A control group was made up of 814 women(median age 29 years) who gave birth at term (>37 weeks gestation)to healthy infants (Apgar 5th minute 8, weight 3000 g) on randomlyselected days at the same hospitals where cases had been identified.A total of 212 cases (46%) and 355 controls (47%) reported alcoholdrinking before conception. Considering non-drinkers as thereference category, the relative risks (RR) of spontaneous abortionwere 1.2 (95% confidence interval (CI), 0.91.6] and 0.8(95% CI, 0.61.1), respectively, in drinkers of one toseven and more than seven drinks per week before conception.No association emerged between the duration of alcohol drinkingand the risk of spontaneous abortion. A total of 166 cases (35.9%)and 263 (32.3%) controls reported any alcohol drinking duringthe first trimester of pregnancy. The corresponding relativerisk was 1.1 (95% CI, 0.91.4) and no relationship emergedbetween the number of drinks per week and the risk of abortion.Likewise, maternal wine and beer drinking in the first trimesterof pregnancy was not associated with the risk of spontaneousabortion. Evidence available from this and previous studies,although partially controversial, indicates that moderate (oneor two drinks per day) alcohol consumption does not increasemarkedly the risk of miscarriage. 相似文献
89.
Genotype-phenotype relationship in human ATP6i-dependent autosomal recessive osteopetrosis 总被引:5,自引:0,他引:5
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)
Taranta A Migliaccio S Recchia I Caniglia M Luciani M De Rossi G Dionisi-Vici C Pinto RM Francalanci P Boldrini R Lanino E Dini G Morreale G Ralston SH Villa A Vezzoni P Del Principe D Cassiani F Palumbo G Teti A 《The American journal of pathology》2003,162(1):57-68
Autosomal-recessive osteopetrosis is a severe genetic disease caused by osteoclast failure. Approximately 50% of the patients harbor mutations of the ATP6i gene, encoding for the osteoclast-specific a3 subunit of V-ATPase. We found inactivating ATP6i mutations in four patients, and three of these were novel. Patients shared macrocephaly, growth retardation and optic nerve alteration, osteosclerotic and endobone patterns, and high alkaline phosphatase and parathyroid hormone levels. Bone biopsies revealed primary spongiosa lined with active osteoblasts and high numbers of tartrate-resistant acid phosphatase (TRAP)-positive, a3 subunit-negative, morphologically unremarkable osteoclasts, some of which located in shallow Howship lacunae. Scarce hematopoietic cells and abundant fibrous tissue containing TRAP-positive putative osteoclast precursors were noted. In vitro osteoclasts were a3-negative, morphologically normal, with prominent clear zones and actin rings, and TRAP activity more elevated than in control patients. Podosomes, alphaVbeta3 receptor, c-Src, and PYK2 were unremarkable. Consistent with the finding in the bone biopsies, these cells excavated pits faintly stained with toluidine blue, indicating inefficient bone resorption. Bone marrow transplantation was successful in all patients, and posttransplant osteoclasts showed rescue of a3 subunit immunoreactivity. 相似文献
90.
Ricca V Nacmias B Boldrini M Cellini E di Bernardo M Ravaldi C Tedde A Bagnoli S Placidi GF Rotella CM Sorbi S 《Neuroscience letters》2004,365(2):92-96
Various studies have evaluated the possible role of the -1438G/A polymorphism within the 5-HT2A receptor gene in the susceptibility to Eating Disorders (EDs). One hundred and forty-eight ED patients (EDp) and 89 control subjects were interviewed by means of the Eating Disorder Examination (EDE) and analyzed for distribution of the -1438G/A polymorphism. Patients with the AA genotype suffering from Anorexia Nervosa and Bulimia Nervosa showed higher Weight and Shape Concern (P = 0.003 and P = 0.010, respectively) scores and greater overall severity of the ED psychopathology (EDE total score) (P = 0.012). The obtained preliminary data suggest the use of dimensional psychopathological measures in ED genetic studies. 相似文献