全文获取类型
收费全文 | 16679篇 |
免费 | 1133篇 |
国内免费 | 80篇 |
专业分类
耳鼻咽喉 | 224篇 |
儿科学 | 319篇 |
妇产科学 | 326篇 |
基础医学 | 2647篇 |
口腔科学 | 1092篇 |
临床医学 | 1441篇 |
内科学 | 3793篇 |
皮肤病学 | 407篇 |
神经病学 | 1403篇 |
特种医学 | 305篇 |
外科学 | 1836篇 |
综合类 | 45篇 |
一般理论 | 6篇 |
预防医学 | 1580篇 |
眼科学 | 165篇 |
药学 | 1271篇 |
中国医学 | 156篇 |
肿瘤学 | 876篇 |
出版年
2023年 | 176篇 |
2022年 | 350篇 |
2021年 | 636篇 |
2020年 | 377篇 |
2019年 | 514篇 |
2018年 | 634篇 |
2017年 | 462篇 |
2016年 | 523篇 |
2015年 | 605篇 |
2014年 | 740篇 |
2013年 | 991篇 |
2012年 | 1398篇 |
2011年 | 1575篇 |
2010年 | 784篇 |
2009年 | 659篇 |
2008年 | 1036篇 |
2007年 | 1028篇 |
2006年 | 915篇 |
2005年 | 828篇 |
2004年 | 690篇 |
2003年 | 608篇 |
2002年 | 550篇 |
2001年 | 236篇 |
2000年 | 230篇 |
1999年 | 199篇 |
1998年 | 91篇 |
1997年 | 79篇 |
1996年 | 51篇 |
1995年 | 53篇 |
1994年 | 53篇 |
1993年 | 42篇 |
1992年 | 96篇 |
1991年 | 68篇 |
1990年 | 67篇 |
1989年 | 63篇 |
1988年 | 41篇 |
1987年 | 31篇 |
1986年 | 32篇 |
1985年 | 38篇 |
1984年 | 23篇 |
1983年 | 18篇 |
1980年 | 21篇 |
1979年 | 16篇 |
1978年 | 22篇 |
1975年 | 17篇 |
1973年 | 22篇 |
1971年 | 21篇 |
1970年 | 17篇 |
1969年 | 19篇 |
1967年 | 15篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
81.
Creutzfeldt-Jakob disease (CJD) with a mutation at codon 148 of prion protein gene: relationship with sporadic CJD 总被引:1,自引:0,他引:1
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)
Pastore M Chin SS Bell KL Dong Z Yang Q Yang L Yuan J Chen SG Gambetti P Zou WQ 《The American journal of pathology》2005,167(6):1729-1738
Creutzfeldt-Jakob disease (CJD), the most common human prion disease, includes sporadic (s) and familial (f) forms. Regardless of etiology, both forms are thought to share the pathogenic mechanism whereby the cellular prion protein (PrP(C)) converts into its pathogenic isoform (PrP(Sc)). While PrP(C) conversion is thought to be random in sCJD, conversion in fCJD is facilitated by the congenital presence of mutated PrP. Differences in PrP genotype (PRNP) and in conversion circumstances lead to PrP(Sc) with distinct characteristics that elicit different disease phenotypes. Here, we describe a case of fCJD with a substitution of histidine (H) for arginine (R) at codon 148 (R148H) and heterozygosity of the methionine/valine (M/V) polymorphic codon 129, with the 129M allele coupled with the mutation. The disease phenotype and all major characteristics of PrP(Sc) of fCJD(R148H) were virtually indistinguishable from those of sCJDMV2, which has features different from those of any other sCJD. Therefore, despite the differences in etiology, PRNP, and conversion process, the two forms of PrP(Sc) had similar characteristics. Furthermore, comparison of fCJD(R148H) with a recently reported case carrying R148H and homozygosity at codon 129 suggests that codon 129 coupled with the mutation as well as that located on the normal allele can modify major phenotypic and PrP(Sc) features of fCJD(R148H). 相似文献
82.
CD40 is required for the optimal induction of protective immunity to Mycobacterium avium 总被引:1,自引:0,他引:1
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)
C57Bl/6 mice and mice deficient in the CD40 molecule were infected with three strains of Mycobacterium avium. Two of the M. avium strains proliferated more extensively in CD40-deficient (CD40-/-) mice than in control mice. The increased susceptibility to infection of CD40-/- mice was associated with the generation of poorer interleukin-12 (IL-12) p40 and interferon-gamma (IFN-gamma) responses as compared to the controls, suggesting a role for CD40 in the development of protective immunity. In contrast, direct triggering of CD40 on infected macrophages failed to induce any anti-mycobacterial activity in infected macrophages. 相似文献
83.
Determination of Blomia tropicalis-specific IgE and IgG subclasses in atopic dermatitis patients 总被引:2,自引:0,他引:2
BACKGROUND: To verify the importance of Blomia tropicalis in atopic dermatitis (AD), we determined the cutaneous reactivity and the serum level of B. tropicalis-specific IgE and IgG subclasses in AD patients. METHODS: B. tropicalis-specific IgE and IgG subclasses were determined in AD patients and compared with bronchial asthma (BA) patients and a control group (CG) of nonatopic subjects. Specific IgE was obtained by skin prick test and RAST. B. tropicalis-specific IgG subclasses were determined by ELISA. The data were statistically analyzed by chi-square test (Mantel-Haenszel) and odds ratio (OR). RESULTS: We detected positive skin prick tests in 61.76% of AD and 83.33% of BA patients, and in 12.5% of the CG. RAST was positive in 44.12% of AD and in 61.90% of BA patients, but not in the CG. B. tropicalis-specific IgG1 and IgG2 subclasses showed no significant differences between the three groups. IgG3 subclass positivity was statistically significant in AD patients (41.17%) when compared to BA patients (14.29%) and the CG (16.67%). The determination of B. tropicalis-specific IgG4 was positive in 32.35% of AD patients, 21.43% of BA patients, and 8.33% of the CG. CONCLUSIONS: These results confirm that the storage mite B. tropicalis is an important allergen in AD. It is possible that IgG3 activates the complement in AD patients, releasing vasoactive amines that further amplify the allergic reaction. The positive results of the B. tropicalis-specific IgG4 found in AD and BA were probably due to chronic exposure to this storage mite in the home environment. 相似文献
84.
Emergence of nonencapsulated and encapsulated non-b-type invasive Haemophilus influenzae isolates in Portugal (1989-2001)
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)
Phenotypes and genetic relatedness of invasive Haemophilus influenzae strains were evaluated from 1989 through 2001. Among 119 isolates, multidrug resistance decreased (from 50 to 0%), the level of H. influenzae serotype b (Hib) strains declined (from 81 to 16%), the level of noncapsulated strains rose (from 19 to 80%), and the first invasive H. influenzae serotype f strain was described. This study documents changes in invasive H. influenzae infections in Portugal, i.e., the emergence of non-type-b strains that are genetically diverse and unrelated to Hib. 相似文献
85.
The infection of tumor necrosis factor (TNF)-deficient mice with low doses of the virulent Mycobacterium avium strain 25291 led to the appearance of necrotic granulomas at 93 days of infection, i.e., sooner than necrotic granulomas appeared in C57BL/6 animals. Additionally, TNF-deficient mice exhibited higher mycobacterial loads in the infected organs, had extremely exacerbated gamma interferon responses as evaluated in the sera of infected animals, and showed reduced survival. Thus, TNF is not required for granuloma necrosis. 相似文献
86.
Simultaneous immunization of mice with an Ascaris suum extract (Asc) and ovalbumin (OA) markedly affects the immune response to OA. The role of interleukin (IL)-4 and IL-10 induced by Asc immunization on the modulation of antigen-specific and mitogen-induced responses was investigated following single or combined cytokine-specific monoclonal antibody (MoAb) treatment of mice before immunization with OA + Asc. Immediate hypersensitivity reactions to aggregated OA and OA-specific immunoglobulin (Ig)G2a antibody production were completely restored only when both IL-4 and IL-10 were neutralized. These findings were associated with enhanced interferon (IFN)-γ secretion by OA-stimulated lymph node (LN) cells. In addition, the Asc-specific cytokine response in anti-IL-4 plus anti-IL-10 MoAb treated mice was shifted towards a Th1 phenotype, with an increase in IFN-γ and IL-2 levels and a decrease in IL-4, but not in IL-10, levels. Consequently, Asc-specific IgG2a antibody production increased, whereas IgE titres diminished in these animals. These results indicate that IL-4 and IL-10 act together in the Asc-induced mechanism of antigen-specific pansuppression. In contrast, modulation of Concanavalin A (Con A)-induced cytokine responses in Asc-immunized mice appears to be essentially mediated by an IL-4-dependent mechanism, since the neutralization of just IL-4 (and not of IL-10), either in vivo or in vitro , changed the cytokine profile from a Th2 towards a Th1 type. However, OA and Asc-specific cell responses were not modified by either anti-IL-4 or by anti-IL-4 + anti-IL-10 MoAbs in vitro treatments, suggesting that the induction of a Th2 response to Asc components concomitant to OA immunization has a strong suppressive effect on the priming stage of OA-specific Th1 type response. 相似文献
87.
Cl udia M. D. da Silva Henrique B. Ferreira Marina Pic n Nicole Gorfinkiel Ricardo Ehrlich Arnaldo Zaha 《Molecular and biochemical parasitology》1993,60(2):209-219
An Echinococcus granulosus genomic library has been screened with a mouse β-actin cDNA probe. Two clones carrying DNA fragments of about 15 kb, possibly derived from the same genome region, have been isolated. This 15-kb genomic region includes 2 actin-related sequences (EgactI and EgactII) separated by about 4 kb. The nucleotide sequences of both genes were determined. The EgactI sequence presents no introns, but an intron of 591 bp was observed in the EgactII sequence. The genes potentially encode 375 and 376 amino-acid-long actins, respectively, with a homology of 85.3%. The deduced amino acid sequences from both genes were compared to the actin sequences from other organisms, showing similarities ranging from 63.5% to 90.6%. The nucleotide sequence of a partial actin cDNA clone has been determined. The deduced amino acids sequence showed a homology of 90.3% and 88.0% in relation to the EgactI and EgactII sequences respectively, suggesting the existence of at least one more actin gene in E. granulosus. This hypothesis is reinforced by the number of bands detected in the Southern blot analysis. Experiments based on the amplification of DNA segments using 3′-specific actin primers indicate that the EgactI gene is transcribed in protoscoleces. 相似文献
88.
89.
The Vi capsular antigen of Salmonella enterica serotype Typhi reduces Toll-like receptor-dependent interleukin-8 expression in the intestinal mucosa 总被引:5,自引:1,他引:5
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)
Raffatellu M Chessa D Wilson RP Dusold R Rubino S Bäumler AJ 《Infection and immunity》2005,73(6):3367-3374
Human infections with nontyphoidal Salmonella serotypes, such as S. enterica serotype Typhimurium, are characterized by a massive neutrophil influx in the colon and terminal ileum. In contrast, neutrophils are scarce in intestinal infiltrates of typhoid fever patients. Here, we show that in S. enterica serotype Typhi, the causative agent of typhoid fever, expression of the Vi capsular antigen reduced expression of the neutrophil chemoattractant interleukin-8 (IL-8) in host cells. Capsulated bacteria elicited IL-8 expression in polarized human epithelial cells (T84) and human macrophage-like cells (THP-1) in vitro at significantly reduced levels compared to noncapsulated bacteria. Experiments with a human cell line (HEK293) transfected with human Toll-like receptors (TLRs) demonstrated that in the presence of TLR5 or TLR4/MD2/CD14, a noncapsulated serotype Typhi mutant was able to induce the expression of IL-8, while this host response was significantly reduced when cells were infected with the capsulated serotype Typhi wild type. The relevance of these in vitro observations for the interaction of serotype Typhi with its human host was further studied ex vivo using human colonic tissue explants. Expression of IL-8 was detected in human colonic tissue explants infected with serotype Typhimurium or a noncapsulated serotype Typhi mutant. In contrast, infection with the serotype Typhi wild type did not elicit IL-8 expression in colonic tissue explants. Collectively, these data suggest that the scarcity of neutrophils in intestinal infiltrates of typhoid fever patients is due to a capsule-mediated reduction of TLR-dependent IL-8 production in the intestinal mucosa. 相似文献
90.
Guido Martignoni Maurizio Pea Matteo Brunelli Marco Chilosi Alberto Zamó Manuela Bertaso Paolo Cossu-Rocca John N Eble Gregor Mikuz Giacomo Puppa Cecile Badoual Vincenzo Ficarra Giovanni Novella Franco Bonetti 《Modern pathology》2004,17(12):1455-1463
CD10 has been considered a useful marker in the diagnosis of renal carcinomas, because of its expression in clear cell and papillary renal cell carcinomas and its absence in chromophobe renal cell carcinomas. On the other hand, chromophobe renal cell carcinoma expresses parvalbumin, which is absent in clear cell and papillary renal cell carcinomas. To further address the relevance of these markers, we studied the expression of CD10 and parvalbumin in 42 samples of chromophobe renal cell carcinoma (seven of which had aggressive features, including invasion beyond the renal capsule, renal vein invasion, metastases, or sarcomatoid transformation), 75 clear cell renal cell carcinomas (eight metastatic) and 51 papillary renal cell carcinomas (two metastatic). CD10 was found in 100% of clear cell renal cell carcinomas, 63% of papillary renal cell carcinomas and in all metastatic cases of both types. At variance with previous studies, we found CD10 expression in from 30 to 90% of the neoplastic cells, in 11 of 42 (26%) chromophobe renal cell carcinomas. The CD10-positive cases included five of the seven (71%) chromophobe renal cell carcinoma with aggressive features. Statistical analysis showed significant association of CD10-positive tumors with clinicopathologic aggressiveness (P=0.003) and mitotic figures (P=0.04). Parvalbumin was strongly expressed in all primary and metastatic chromophobe renal cell carcinomas. Western blot analysis was utilized to confirm the expression of both CD10 and parvalbumin in chromophobe renal cell carcinomas. 相似文献