全文获取类型
收费全文 | 11843篇 |
免费 | 1238篇 |
国内免费 | 85篇 |
专业分类
耳鼻咽喉 | 72篇 |
儿科学 | 479篇 |
妇产科学 | 378篇 |
基础医学 | 1687篇 |
口腔科学 | 236篇 |
临床医学 | 1341篇 |
内科学 | 2477篇 |
皮肤病学 | 170篇 |
神经病学 | 842篇 |
特种医学 | 712篇 |
外科学 | 1509篇 |
综合类 | 343篇 |
一般理论 | 7篇 |
预防医学 | 1162篇 |
眼科学 | 120篇 |
药学 | 936篇 |
2篇 | |
中国医学 | 3篇 |
肿瘤学 | 690篇 |
出版年
2021年 | 149篇 |
2020年 | 108篇 |
2019年 | 161篇 |
2018年 | 176篇 |
2017年 | 153篇 |
2016年 | 140篇 |
2015年 | 199篇 |
2014年 | 289篇 |
2013年 | 390篇 |
2012年 | 503篇 |
2011年 | 543篇 |
2010年 | 350篇 |
2009年 | 322篇 |
2008年 | 466篇 |
2007年 | 510篇 |
2006年 | 475篇 |
2005年 | 458篇 |
2004年 | 417篇 |
2003年 | 386篇 |
2002年 | 397篇 |
2001年 | 354篇 |
2000年 | 362篇 |
1999年 | 326篇 |
1998年 | 249篇 |
1997年 | 265篇 |
1996年 | 258篇 |
1995年 | 214篇 |
1994年 | 212篇 |
1993年 | 203篇 |
1992年 | 254篇 |
1991年 | 283篇 |
1990年 | 254篇 |
1989年 | 243篇 |
1988年 | 259篇 |
1987年 | 270篇 |
1986年 | 249篇 |
1985年 | 248篇 |
1984年 | 180篇 |
1983年 | 153篇 |
1982年 | 116篇 |
1981年 | 110篇 |
1980年 | 89篇 |
1979年 | 108篇 |
1978年 | 93篇 |
1977年 | 95篇 |
1976年 | 95篇 |
1975年 | 92篇 |
1973年 | 89篇 |
1972年 | 85篇 |
1971年 | 77篇 |
排序方式: 共有10000条查询结果,搜索用时 921 毫秒
111.
Mutation analysis of the spastin gene (SPG4) in patients with hereditary spastic paraparesis 总被引:8,自引:2,他引:8
下载免费PDF全文
![点击此处可从《Journal of medical genetics》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Lindsey JC Lusher ME McDermott CJ White KD Reid E Rubinsztein DC Bashir R Hazan J Shaw PJ Bushby KM 《Journal of medical genetics》2000,37(10):759-765
BACKGROUND—Hereditary spastic paraparesis is a genetically heterogeneous condition. Recently, mutations in the spastin gene were reported in families linked to the common SPG4 locus on chromosome 2p21-22.
OBJECTIVES—To study a population of patients with hereditary spastic paraparesis for mutations in the spastin gene (SPG4) on chromosome 2p21-22.
METHODS—DNA from 32 patients (12 from families known to be linked to SPG4) was analysed for mutations in the spastin gene by single strand conformational polymorphism analysis and sequencing. All patients were also examined clinically.
RESULTS—Thirteen SPG4 mutations were identified, 11 of which are novel. These mutations include missense, nonsense, frameshift, and splice site mutations, the majority of which affect the AAA cassette. We also describe a nucleotide substitution outside this conserved region which appears to behave as a recessive mutation.
CONCLUSIONS—Recurrent mutations in the spastin gene are uncommon. This reduces the ease of mutation detection as a part of the diagnostic work up of patients with hereditary spastic paraparesis. Our findings have important implications for the presumed function of spastin and schemes for mutation detection in HSP patients.
Keywords: spastin; hereditary spastic paraparesis; mutation; recessive 相似文献
OBJECTIVES—To study a population of patients with hereditary spastic paraparesis for mutations in the spastin gene (SPG4) on chromosome 2p21-22.
METHODS—DNA from 32 patients (12 from families known to be linked to SPG4) was analysed for mutations in the spastin gene by single strand conformational polymorphism analysis and sequencing. All patients were also examined clinically.
RESULTS—Thirteen SPG4 mutations were identified, 11 of which are novel. These mutations include missense, nonsense, frameshift, and splice site mutations, the majority of which affect the AAA cassette. We also describe a nucleotide substitution outside this conserved region which appears to behave as a recessive mutation.
CONCLUSIONS—Recurrent mutations in the spastin gene are uncommon. This reduces the ease of mutation detection as a part of the diagnostic work up of patients with hereditary spastic paraparesis. Our findings have important implications for the presumed function of spastin and schemes for mutation detection in HSP patients.
Keywords: spastin; hereditary spastic paraparesis; mutation; recessive 相似文献
112.
Fiona Reid Jaythoon Hassan Fiona Irwin Allison Waters William Hall Jeff Connell 《Journal of clinical virology》2008,41(2):134-137
OBJECTIVE: To determine the optimal strategy to investigate mumps virus infection in a partially vaccinated cohort. STUDY DESIGN: 122 oral fluid and serum samples were collected in a recent outbreak in Ireland. The largest age cohort, students aged 18-21 years old attending third level institutions, were investigated using virus isolation, detection of mumps specific IgM, IgG, RT-PCR and molecular genotyping. RESULTS: 97% of patients had both detectable serum IgM and IgG. Mumps virus RNA was detected in 17 oral fluid samples and 14 of these originated from a single geographic location. Only 6 of the IgM positive samples had detectable mumps virus RNA whereas this could be detected in 11 IgM negative samples. Genotyping studies revealed that genotypes G and J were co-circulating during this outbreak. CONCLUSIONS: The use of an oral fluid sample to detect mumps virus RNA and IgM offers a major improvement over serological diagnosis in acute infection in both non-vaccinated or partially vaccinated individuals, and has the advantage that specimens are collected non-invasively. 相似文献
113.
Liñares D Mañá P Goodyear M Chow AM Clavarino C Huntington ND Barnett L Koentgen F Tomioka R Bernard CC Freire-Garabal M Reid HH 《Journal of autoimmunity》2003,21(4):339-351
Myelin oligodendrocyte glycoprotein (MOG) is a minor component of central nervous system myelin presumably implicated in the pathogenesis of Multiple Sclerosis (MS). Immunization with MOG leads to the development of Experimental Autoimmune Encephalomyelitis (EAE), the experimental model of MS. It has been suggested that its encephalitogenic potential may be due to the lack of MOG self-immune tolerance. To clarify this, we have generated a MOG deficient mouse (MOG(-/-)) strain. Surprisingly, MOG(35-55)specific proliferation and Th1-type cytokine production were markedly enhanced in MOG(-/-)mice compared to wild type control. Furthermore, adoptive transfer of MOG(35-55)specific T cells, isolated from MOG deficient mice, into wild-type recipients resulted in the development of a more severe disease, indicating a high capacity of MOG(-/-)T cells to initiate effector responses. Interestingly, T cell reactivity to overlapping MOG peptides in MOG(-/-)mice did not reveal new potential immunodominant epitopes in H-2(b)mice. Taken together, our data suggests that MOG self-tolerance modulates the encephalitogenic potential of autoreactive MOG T cells in the periphery. 相似文献
114.
115.
Fine specificity of autoantibodies to calreticulin: epitope mapping and characterization 总被引:2,自引:0,他引:2
下载免费PDF全文
![点击此处可从《Clinical and experimental immunology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Eggleton P Ward FJ Johnson S Khamashta MA Hughes GR Hajela VA Michalak M Corbett EF Staines NA Reid KB 《Clinical and experimental immunology》2000,120(2):384-391
Extracellular calreticulin (CRT) as well as anti‐CRT antibodies have been reported in patients with various autoimmune disorders and CRT has been implicated in ‘epitope spreading’ to other autoantigens such as the Ro/SS‐A complex. In addition, antibodies against parasite forms of the endoplasmic reticulum chaperone, CRT, have been found in patients suffering from onchocerciasis and schistosomiasis. In this study, we screened sera for anti‐CRT antibodies from patients with active and inactive systemic lupus ertythematosus (SLE) and primary or secondary Sjögren’s syndrome. Approximately 40% of all SLE patients were positive for anti‐CRT antibodies. The antigenic regions of CRT were determined using full length CRT and fragments of CRT prepared in yeast and Escherichia coli, respectively. Synthetic 15mer peptides corresponding to the major autoantigenic region of CRT (amino acids 1–289), each one overlapping by 12 amino acids, were used to map the B cell epitopes on the CRT protein recognized by autoimmune sera. Major antigenic epitopes were found to be associated with the N‐terminal half of the protein in 69% of the SLE sera from active disease patients, while the C‐domain was not antigenic. Major epitopes were found to be reactive with antibodies in sera from SLE patients with both active and inactive disease, spanning different regions of the N and P‐domains. Sera from both healthy and disease controls and primary Sjögren’s syndrome patients were non‐reactive to these sequences. Limited proteolysis of CRT with two major leucocyte serine proteases, elastase and cathepsin G, demonstrated that an N‐terminal region of CRT is resistant to digestion. Interestingly, some of the epitopes with the highest reactivity belong to the fragments of the protein which bind to C1q and inhibit complement activation. Whether C1q association with CRT is a pathological or protective interaction between these two proteins is currently under investigation. 相似文献
116.
Immune-stimulating complexes containing Quil A and protein antigen prime class I MHC-restricted T lymphocytes in vivo and are immunogenic by the oral route 总被引:7,自引:0,他引:7
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)
Induction of all forms of protective immunity by oral immunization with subunit vaccines is an ideal goal for the development of novel vaccines, but creates several theoretical problems from the point of view of antigen processing mechanisms. We show here that incorporation of the protein antigen ovalbumin (OVA) in lipophilic immune-stimulating complexes (ISCOMS) induces very strong primary immune responses in mice and requires very small amounts of antigen. OVA ISCOMS were particularly efficient at stimulating T-cell-mediated immunity in vivo, including delayed-type hypersensitivity (DTH) and potent class I major histocompatibility complex (MHC)-restricted cytotoxic T-cell responses. Furthermore, unlike native protein, OVA in ISCOMS was immunogenic when given orally. Thus, ISCOMS seem to allow protein to enter both the endogenous and exogenous pathways of antigen processing and overcome the usual induction of tolerance after feeding antigen. ISCOMS could provide potentially useful adjuvants for the development of oral subunit vaccines. 相似文献
117.
M Avellanet RM Mirapeix D Escudero C Riera JM Domenech-Mateu 《Surgical and radiologic anatomy : SRA》1996,18(4):271-273
Summary We present a case with a characteristic magnetic resonance image (MRI) of bilateral open-lipped schizencephaly and atypical clinical presentation. The patient is still alive and in good health in her forties, she has never presented seizures, and although the motor dysfunction is well correlated with cerebral lobe involvement, neurobehavioral dysfunction is not proportional to the MR image of the cerebral malformation.
Un cas inhabituel de schizencéphalie bilatérale
Résumé Nous présentons un cas de schizencéphalie bilatérale ouverte caractérisé par une présentation clinique atypique et une imagerie par résonance magnétique nucléaire caractéristique. La patiente est encore vivante, en bonne santé, à plus de 40 ans, elle n'a jamais présenté de crise comitiale et, bien que les troubles moteurs soient bien corrélés aux altérations cérébrales, les troubles neuro-comportementaux ne sont pas proportionnels aux images IRM de cette malformation cérébrale.相似文献
118.
J. M. Reid D. J. Paterson F. M. Ashcroft D. H. Bergel 《Pflügers Archiv : European journal of physiology》1993,425(3-4):362-364
The increase in blood flow in the cerebral cortex of the anaesthetized rat during hypoxia and hypercapnia was investigated. Cerebral blood flow (CBF) was measured using the hydrogen clearance method with acutely implanted platinum electrodes. Hypoxia (PaO2 35.3±2.4 Torr) and hypercapnia (PaCO2 68.1±5.1 Torr) increased basal CBF from 76.3±9.0 ml/100g/min to 168.1±20.1 ml/100g/min and 162.4±31.9 ml/100g/min respectively. The sulphonylurea tolbutamide (1mM in 1%DMSO) had no significant effect on CBF in hyperoxia or in hypercapnia. However, it attenuated the increase of CBF during hypoxia by 66 ±11% (P<0.01). This suggests that opening of tolbutamide-sensitive potassium channels may be involved in the process of hypoxic vasodilation in the rat cerebral cortex. 相似文献
119.
Tissue sections and cultured lymphocytes from rabbits clinically affected following experimental infection with Alcelaphine herpesvirus-1 (AHV-1) were assessed for the presence of viral DNA by in situ hybridization with the cloned major HindII repeat sequence of this virus. Small numbers of virus-infected cells were consistently detected only in submandibular lymph nodes, while other tissues showed no evidence of viral DNA. Virus titration in culture suggested that there were higher titres of virus in the lymph nodes, spleen and lung of infected animals than in the kidney or peripheral blood lymphocytes and confirmed the low level of virus in these animals. Substantially more viral DNA was detected by in situ hybridization in lymphocytes following at least 24 h of culture, suggesting that viral replication is normally repressed by the host. 相似文献
120.
Evaluation of PCR testing of ethanol-fixed nasal swab specimens as an augmented surveillance strategy for influenza virus and adenovirus identification
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)
Krafft AE Russell KL Hawksworth AW McCall S Irvine M Daum LT Connoly JL Reid AH Gaydos JC Taubenberger JK 《Journal of clinical microbiology》2005,43(4):1768-1775
Viral culture isolation has been widely accepted as the "gold standard" for laboratory confirmation of viral infection; however, it requires ultralow temperature specimen storage. Storage of specimens in ethanol at room temperature could expand our ability to conduct active surveillance and retrospective screenings of viruses with rapid and inexpensive real-time PCR tests, including isolates from remote regions where freezing specimens for culture is not feasible. Molecular methods allow for rapid identification of viral pathogens without the need to maintain viability. We hypothesized that ethanol, while inactivating viruses, can preserve DNA and RNA for PCR-based methods. To evaluate the use of ethanol-stored specimens for augmenting surveillance for detection of influenza viruses A and B and adenoviruses (AdV), paired nasal swab specimens were collected from 384 recruits with febrile respiratory illness at Fort Jackson, S.C., in a 2-year study. One swab was stored at ambient temperature in 100% ethanol for up to 6 months, and the other swab was stored at -70 degrees C in viral medium. For viral detection, frozen specimens were cultured for a variety of respiratory viruses, and ethanol-fixed specimens were tested with TaqMan (TM) probe and LightCycler SYBR green (SG) melting curve assays with at least two different PCR targets for each virus. The sensitivities of the TM and SG assays on specimens stored in ethanol for 1 month were 75% and 58% for influenza A, 89% and 67% for influenza B, and 93 to 98% and 57% for AdV, respectively. Lower specificities of the real-time assays corresponded to the increased detection of PCR-positive but culture-negative specimens. Influenza virus RNA was detected as well or better after 6 months of storage in ethanol. 相似文献