全文获取类型
收费全文 | 11508篇 |
免费 | 781篇 |
国内免费 | 46篇 |
专业分类
耳鼻咽喉 | 77篇 |
儿科学 | 303篇 |
妇产科学 | 249篇 |
基础医学 | 1931篇 |
口腔科学 | 97篇 |
临床医学 | 1052篇 |
内科学 | 2613篇 |
皮肤病学 | 187篇 |
神经病学 | 1272篇 |
特种医学 | 301篇 |
外科学 | 1148篇 |
综合类 | 51篇 |
一般理论 | 1篇 |
预防医学 | 897篇 |
眼科学 | 214篇 |
药学 | 761篇 |
中国医学 | 20篇 |
肿瘤学 | 1161篇 |
出版年
2024年 | 10篇 |
2023年 | 101篇 |
2022年 | 159篇 |
2021年 | 336篇 |
2020年 | 215篇 |
2019年 | 316篇 |
2018年 | 407篇 |
2017年 | 249篇 |
2016年 | 246篇 |
2015年 | 314篇 |
2014年 | 451篇 |
2013年 | 581篇 |
2012年 | 984篇 |
2011年 | 980篇 |
2010年 | 517篇 |
2009年 | 548篇 |
2008年 | 840篇 |
2007年 | 864篇 |
2006年 | 758篇 |
2005年 | 765篇 |
2004年 | 672篇 |
2003年 | 657篇 |
2002年 | 633篇 |
2001年 | 72篇 |
2000年 | 62篇 |
1999年 | 67篇 |
1998年 | 94篇 |
1997年 | 94篇 |
1996年 | 69篇 |
1995年 | 52篇 |
1994年 | 47篇 |
1993年 | 39篇 |
1992年 | 20篇 |
1991年 | 14篇 |
1990年 | 11篇 |
1989年 | 8篇 |
1988年 | 11篇 |
1987年 | 7篇 |
1986年 | 9篇 |
1985年 | 3篇 |
1984年 | 4篇 |
1983年 | 4篇 |
1982年 | 5篇 |
1981年 | 3篇 |
1979年 | 4篇 |
1978年 | 3篇 |
1968年 | 3篇 |
1964年 | 3篇 |
1947年 | 2篇 |
1942年 | 2篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
51.
Cloning and characterization of a gene encoding an immunoglobulin-binding receptor on the cell surface of some members of the family Trypanosomatidae
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)
Campos-Neto A Suffia I Cavassani KA Jen S Greeson K Ovendale P Silva JS Reed SG Skeiky YA 《Infection and immunity》2003,71(9):5065-5076
Several members of the Trypanosomatidae family, when freshly isolated from their mammalian hosts, have immunoglobulins adsorbed to their cell surfaces. However, a significant portion of these antibody molecules is not parasite specific, i.e., the immunoglobulins are bound to the parasite's cell surface molecules via noncognitive interactions. It has been proposed that this noncognitive adsorption of immunoglobulins to the parasite is mediated by an Fc-like receptor present in several members of the Trypanosomatidae family. However, the molecular identification of this receptor has never been defined. Here, we describe the cloning of a gene encoding a protein that might represent this molecule. The gene, named Lmsp1, was cloned by screening a Leishmania major cDNA expression library using a rabbit antiserum. Lmsp1 is present in both Leishmania and Trypanosoma and is expressed in all developmental stages of these parasites. The predicted protein has a molecular mass of 16.6 kDa and contains an RGD sequence starting at residue 104 and three cysteine residues at positions 55, 74, and 116. The purified recombinant protein strongly binds to normal immunoglobulins of various animal species (humans, rabbits, sheep, goats, guinea pigs, donkeys, rats, and mice) and the binding to human immunoglobulins appears to be immunoglobulin G (IgG) and IgM isotype specific. Moreover, Lmsp1 binds to both purified Fc and Fab fragments of IgG from both humans and rabbits. The mapping of the Lmsp1 epitopes that bind human IgG revealed that different sequences of the molecule bind to Fc or Fab. In addition, fluorescence-activated cell sorter analyses with a specific rabbit anti-Lmsp1 antiserum showed that Lmsp1 is associated with the parasite's cell surface. Finally, inhibition experiments point to an active role of this molecule in the immunoglobulin-mediated attachment and penetration of Trypanosoma cruzi in its macrophage host cells, thus suggesting that Lmsp1 is a putative Trypanosomatidae immunoglobulin receptor. 相似文献
52.
Papadimitriou GN Dikeos DG Souery D Del-Favero J Massat I Avramopoulos D Blairy S Cichon S Ivezic S Kaneva R Karadima G Lilli R Milanova V Nöthen M Oruc L Rietschel M Serretti A Van Broeckhoven C Stefanis CN Mendlewicz J 《Psychiatric genetics》2003,13(4):211-220
The co-segregation in one pedigree of bipolar affective disorder with Darier's disease whose gene is on chromosome 12q23-q24.1, and findings from linkage and association studies with the neighbouring gene of phospholipase A2 (PLA2) indicate that PLA2 may be considered as a candidate gene for affective disorders. All relevant genetic association studies, however, were conducted on bipolar patients. In the present study, the possible association between the PLA2 gene and unipolar affective disorder was examined on 321 unipolar patients and 604 controls (all personally interviewed), recruited from six countries (Belgium, Bulgaria, Croatia, Germany, Greece, and Italy) participating in the European Collaborative Project on Affective Disorders. After controlling for population group and gender, one of the eight alleles of the investigated marker (allele 7) was found to be more frequent among unipolar patients with more than three major depressive episodes than among controls (P<0.01); genotypic association was also observed, under the dominant model of genetic transmission (P<0.02). In addition, presence of allele 7 was correlated with a higher frequency of depressive episodes (P<0.02). These findings suggest that structural variations at the PLA2 gene or the chromosomal region around it may confer susceptibility for unipolar affective disorder. 相似文献
53.
Schleiermacher G Raynal V Janoueix-Lerosey I Combaret V Aurias A Delattre O 《Genes, chromosomes & cancer》2004,39(2):143-150
In neuroblastoma, the most frequent genetic alteration is gain of chromosome arm 17q, which arises from unbalanced translocations. To document these genetic events more precisely, we performed an extensive study of chromosome 17 breakpoints in 27 neuroblastoma cell lines by using a combination of fluorescence in situ hybridization mapping with BAC/PAC clones and allele analysis with polymorphic markers. All cases exhibited one or more unbalanced chromosome 17 translocations, and 15 distinct breakpoint regions could be mapped. This high variability indicates that gene fusion or disruption events are extremely unlikely to account for the underlying oncogenic role of these translocations. However, breakpoints were not randomly distributed, most of them mapping to the proximal part of 17q. As a result of translocations, all cell lines but one exhibited gain of the 53.5 Mb-->qter fragment, bordered proximally by the clone CTC-462L7. The most telomeric breakpoint, flanked by the clone RP11-443M10, defined the 70.9 Mb-->qter fragment as a region of additional gain. In addition to chromosome gains, loss of heterozygosity for the short arm of chromosome 17 was observed in close to half the cases. It was either related to a chromosome 17 monosomy or to a uniparental isodisomy. Finally, in cases with a single normal chromosome 17, we show that the parental origin of the translocated chromosome 17 can be either distinct or identical to that of the normal chromosome. Similarly, multiple translocations within the same cell line can either involve the same or different chromosome 17 homologues, indicating the likely absence of parental origin bias in the generation of these alterations. 相似文献
54.
A Sabin 1 strain poliovirus (PV) mutant, S1(2Y-1I), carrying a Tyr at amino acid position VP2(142) and an Ile at position VP1(160), can establish persistent infections in HEp-2c cells. This mutant forms atypical 147S particles upon interaction at 0 degrees C with either cells expressing PV receptor (PVR) CD155, or PVR-IgG2a, a chimeric molecule consisting of an extracellular moiety of PVR and the hinge and Fc portion of a mouse IgG2a. Upon interaction with PVR at 37 degrees C, S1(2Y-1I), similar to the parental strain, forms both 135S A particles and 80S empty capsids. At 0 degrees C, surprisingly, at a concentration equal to or greater than 5 nM, PVR-IgG2a induced both the extrusion of VP4 from the capsid of S1(2Y-1I) and the formation of 80S particles. The same transitions were observed at 0 degrees C with the parental strain Sabin 1 at 40 nM PVR-IgG2a. Thus, the formation of 80S particles and VP4 extrusion, considered as one of the steps of PV uncoating, can be temperature-independent at high PVR concentration. This implies that structural changes of the PV capsid occurred following adsorption at low temperature. 相似文献
55.
56.
Dezfulian H Batisson I Fairbrother JM Lau PC Nassar A Szatmari G Harel J 《Journal of clinical microbiology》2003,41(4):1375-1385
The virulence genotype profile and presence of a pathogenicity island(s) (PAI) were studied in 18 strains of F165-positive Escherichia coli originally isolated from diseased calves or piglets. On the basis of their adhesion phenotypes and genotypes, these extraintestinal pathogenic strains were classified into three groups. The F165 fimbrial complex consists of at least two serologically and genetically distinct fimbriae: F165(1) and F165(2). F165(1) is encoded by the foo operon (pap-like), and F165(2) is encoded by fot (sfa related). Strains in group 1 were foo and fot positive, strains in group 2 were foo and afa positive, and strains in group 3 were foo positive only. The strains were tested for the presence of virulence genes found mainly in extraintestinal pathogenic E. coli (ExPEC) strains. Although all the strains were positive for the papA variant encoding F11 fimbriae incD, traT, and papC, the prevalence of virulence genes commonly found in PAIs associated with ExPEC strains was highly variable, with strains of group 2 harboring most of the virulence genes tested. papG allele III was detected in all strains in group 1 and in one strain in group 3. All other strains were negative for the known alleles encoding PapG adhesins. The association of virulence genes with tRNA genes was characterized in these strains by using pulsed-field gel electrophoresis and DNA hybridization. The insertion site of the foo operon was found at the pheU tRNA locus in 16 of the 18 strains and at the selC tRNA locus in the other 2 strains. Furthermore, 8 of the 18 strains harbored a high-pathogenicity island which was inserted in either the asnT or the asnV/U tRNA locus. These results suggest the presence of one or more PAIs in septicemic strains from animals and the association of the foo operon with at least one of these islands. F165-positive strains share certain virulence traits with ExPEC, and most of them are pathogenic in piglets, as tested in experimental infections. 相似文献
57.
Specificities and functions of the recA and pps1 intein genes of Mycobacterium tuberculosis and application for diagnosis of tuberculosis
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)
Saves I Lewis LA Westrelin F Warren R Daffé M Masson JM 《Journal of clinical microbiology》2002,40(3):943-950
The worldwide recrudescence of tuberculosis and the widespread appearance of antibiotic resistance have strengthened the need for rapid and specific diagnostic tools. The prevailing microbiological identification of Mycobacterium tuberculosis, the causative agent of tuberculosis, which implies the use of in vitro cultures and acid-fast staining microscopy, is time-consuming. Detection of M. tuberculosis directly in clinical samples through PCR amplification of mycobacterium-specific genes, designed to shorten diagnostic delay, demonstrated reliability and high sensitivity. However, the quality of the diagnosis depends on the specificity of the target sequence for M. tuberculosis complex strains. In the present study, we demonstrated the specificity of recA and pps1 inteins for this complex and thus the feasibility of using intein-coding sequences as a new target for PCR diagnosis. Indeed, the recA and pps1 genes of 36 clinical isolates of M. tuberculosis and 10 field strains of M. bovis were found to be interrupted by an intein sequence at the RecA-a and Pps1-b sites, respectively, while a large number of nontuberculous mycobacterial species failed to demonstrate these insertions. Besides, the MtuPps1, which was cloned and expressed in Escherichia coli, was shown to possess an endonuclease activity. The intein cleaves the 40-bp sequence spanning the intein insertion site Pps1-b in the inteinless pps1 gene. In addition to the PCR amplification of recA and pps1 intein genes as a tool for diagnosis, the specific endonuclease activity could represent a new molecular approach to identify M. tuberculosis. 相似文献
58.
Dominique Bonneau Isabelle Winter-Fuseau Marie-No?lle Loiseau Patrizia Amati Michel Berthier Denis Oriot Carole Beaumont 《Journal of medical genetics》1995,32(10):778-779
This paper reports the cosegregation in a three generation pedigree of dominantly inherited cataract with an abnormally high level of serum ferritin. In this family, circulating L ferritin was raised in all subjects affected by cataract independently of iron overload. We suggest that a disorder of ferritin metabolism could be a new genetic disorder leading to lens opacity. Cataract-hyperferritaemia syndrome could also be a new contiguous gene syndrome involving the L ferritin gene and the gene coding for the lens membrane protein (MP19), which both map to the same region of chromosome 19q. 相似文献
59.
Addition polymerization of hydroxytelechelic polybutadiene (HTPB) with hexamethylene diisocyanate (HMDI) with a mole ratio NCO/OH = 0,8 in dilute solution of toluene as well as in bulk follows apparent 3rd order kinetics. The polymerization rates are twice as sensitive to temperature as in toluene, an effect which is attributed to intra- and/or intermolecular (OH, OH) auto-association. The three alcoholic functions in HTPB are catalyzed equally by dibutyltin dilaurate. Even with high excess of NCO, free alcoholic functions were found in the product. They were determined quantitatively in moulded polyurethane sheets from HTPB + HMDI and HTPB + 4,4′-methylenedi(phenyl isocyanate) which should be partially crosslinked: 相似文献
60.
Murine Dendritic Cells Pulsed In Vitro with Toxoplasma gondii Antigens Induce Protective Immunity In Vivo 总被引:8,自引:0,他引:8
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)
Isabelle Bourguin Muriel Moser Dominique Buzoni-Gatel Franoise Tielemans Daniel Bout Jacques Urbain Oberdan Leo 《Infection and immunity》1998,66(10):4867-4874
The activation of a predominant T-helper-cell subset plays a critical role in disease resolution. In the case of Toxoplasma gondii, the available evidence indicates that CD4+ protective cells belong to the Th1 subset. The aim of this study was to determine whether T. gondii antigens (in T. gondii sonicate [TSo]) presented by splenic dendritic cells (DC) were able to induce a specific immune response in vivo and to protect CBA/J mice orally challenged with T. gondii cysts. CBA/J mice immunized with TSo-pulsed DC exhibited significantly fewer cysts in their brains after oral infection with T. gondii 76K than control mice did. Protected mice developed a strong humoral response in vivo, with especially high levels of anti-TSo immunoglobulin G2a antibodies in serum. T. gondii antigens such as SAG1 (surface protein), SAG2 (surface protein), MIC1 (microneme protein), ROP2 through ROP4 (rhoptry proteins), and MIC2 (microneme protein) were recognized predominantly. Furthermore, DC loaded with TSo, which synthesized high levels of interleukin-12 (IL-12), triggered a strong cellular response in vivo, as assessed by the proliferation of lymph node cells in response to TSo restimulation in vitro. Cellular proliferation was associated with gamma interferon and IL-2 production. Taken together, these results indicate that immunization of CBA/J mice with TSo-pulsed DC can induce both humoral and Th1-like cellular immune responses and affords partial resistance against the establishment of chronic toxoplasmosis. 相似文献