全文获取类型
收费全文 | 22438篇 |
免费 | 1308篇 |
国内免费 | 109篇 |
专业分类
耳鼻咽喉 | 333篇 |
儿科学 | 589篇 |
妇产科学 | 413篇 |
基础医学 | 3296篇 |
口腔科学 | 1674篇 |
临床医学 | 1633篇 |
内科学 | 4813篇 |
皮肤病学 | 627篇 |
神经病学 | 1749篇 |
特种医学 | 491篇 |
外科学 | 2410篇 |
综合类 | 94篇 |
一般理论 | 3篇 |
预防医学 | 2414篇 |
眼科学 | 392篇 |
药学 | 1643篇 |
中国医学 | 221篇 |
肿瘤学 | 1060篇 |
出版年
2023年 | 226篇 |
2022年 | 493篇 |
2021年 | 881篇 |
2020年 | 548篇 |
2019年 | 738篇 |
2018年 | 899篇 |
2017年 | 625篇 |
2016年 | 682篇 |
2015年 | 774篇 |
2014年 | 1008篇 |
2013年 | 1221篇 |
2012年 | 1816篇 |
2011年 | 2006篇 |
2010年 | 1066篇 |
2009年 | 826篇 |
2008年 | 1387篇 |
2007年 | 1295篇 |
2006年 | 1131篇 |
2005年 | 1054篇 |
2004年 | 894篇 |
2003年 | 794篇 |
2002年 | 698篇 |
2001年 | 385篇 |
2000年 | 347篇 |
1999年 | 332篇 |
1998年 | 134篇 |
1997年 | 97篇 |
1996年 | 89篇 |
1995年 | 51篇 |
1994年 | 56篇 |
1993年 | 45篇 |
1992年 | 146篇 |
1991年 | 125篇 |
1990年 | 86篇 |
1989年 | 97篇 |
1988年 | 86篇 |
1987年 | 62篇 |
1986年 | 80篇 |
1985年 | 57篇 |
1984年 | 53篇 |
1983年 | 43篇 |
1982年 | 31篇 |
1981年 | 24篇 |
1980年 | 29篇 |
1979年 | 45篇 |
1978年 | 29篇 |
1977年 | 23篇 |
1976年 | 31篇 |
1971年 | 23篇 |
1969年 | 25篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
81.
Thomazi AP Godinho GF Rodrigues JM Schwalm FD Frizzo ME Moriguchi E Souza DO Wofchuk ST 《Mechanisms of ageing and development》2004,125(7):475-481
The excitotoxicity of the neurotransmitter glutamate has been shown to be connected with many acute and chronic diseases of the CNS. High affinity sodium-dependent glutamate transporters play a key role in maintaining adequate levels of extracellular glutamate. In the present study, we used slices of striatum, hippocampus and cortex from rat brain to describe the in vitro profile of glutamate uptake during development and ageing, and its sensitivity to guanosine. In all structures, glutamate uptake was higher in immature animals. There was a maximum decrease in glutamate uptake in striatum and hippocampus in 15-month-old rats, which later increased, while in cortex there was a significant decrease in rats aged 60 days old. The effect of guanosine seems to be age and structure dependent since the increase in basal glutamate uptake was only seen in slices of cortex from 10-day-old animals. 相似文献
82.
HLA-B44 is the most frequent HLA-B allele in Caucasian populations. Several B44 subtypes, B*4402-B*4406, have been identified in individuals with this ethnic origin. Mismatches among B44 subtypes have been described as major targets for allogeneic responses in bone marrow transplantation. We have developed a PCR-SSO method, based on a B12- specific DNA amplification of exon 2 through exon 3 and subsequent non radioactive hybridization with eight probes, which allow us to discriminate all B12 homozygous combinations. We applied this method to determine the frequency of B44 subtypes in a Spanish population, as well as their HLA-A.-C.-DRB1,-DRB3/DRB4/DRB5.-DQA1 and -DQB1 associated haplotypes. A total of 141 healthy unrelated Spanish individuals and 31 B44-bearing haplotypes were investigated. Four B44 alleles were identified, B*4402 (33%), B*4403 (66%), B*4404 (0.7%), and B*4405 (0.7%). Haplotype analysis showed a clear differentiated distribution pattern for the two major B44 subtypes. B*4402 is associated with Cw5 (11/13) and A2 antigens (10/13). In contrast, B*4403 is mainly found together with DRB1*0701 (14/16). An inverted B*4402/B*4403 frequency in comparison with other European and North American Caucasian populations, revealed the existence of an extended haplotype diversity between populations of the same ethnic origin. Apart from anthropological studies, high resolution typing for HLA class I antigens presenting molecular polymorphism will be of great relevance in unrelated bone marrow transplantation. 相似文献
83.
Evaluation of stromal metalloproteinases and vascular endothelial growth factors in a spontaneous metastasis model 总被引:5,自引:0,他引:5
Donadio AC Durand S Remedi MM Frede S Ceschin DG Genti-Raimondi S Chiabrando GA 《Experimental and molecular pathology》2005,79(3):259-264
This study aims to investigate MMP2 and MT1-MMP protein as well as VEGF-C and VEGF-D mRNA expression in tumor cells and distant organs considered to be targets for metastasis in a tumor spontaneous metastasis model previously described. Cultured tumor cells, able to express pro-MMP2, MMP2, pro-MMP9, and MT1-MMP, develop tumor growth and metastasis, mainly in the liver and spleen, when they are injected in the mammary pad gland of Wistar rats. Immunohistochemical studies of tumor masses showed small groups of tumor cells staining for MT1-MMP but not for MMP2. In the liver, tumor metastatic foci and a stromal positive staining for both MMP2 and MT1-MMP were shown. The spleen and lymph nodes, with only scattered metastatic cells, did not show MMPs immunostaining. Using RT-PCR, a significantly higher VEGF-C and VEGF-D gene expression was shown in the liver of tumor-bearing rats respect to normal rats, whereas spleen and lymph nodes did not show significant differences in mRNA VEGF-C/D levels. Taken together, our results suggest that the stroma microenvironment of target organs for metastasis has the ability to produce MMPs and VEGFs that facilitate the anchorage of tumor cells and promote tumor cell growth and angiogenesis. 相似文献
84.
Angiotensin-(1–7) stimulates water transport in rat inner medullary collecting duct: evidence for involvement of vasopressin V2 receptors 总被引:1,自引:0,他引:1
Magaldi AJ Cesar KR de Araújo M Simões e Silva AC Santos RA 《Pflügers Archiv : European journal of physiology》2003,447(2):223-230
The peptide angiotensin-(1–7) [Ang-(1–7)] is known to enhance water transport in rat inner medullary collecting duct (IMCD). The aim of this study was to determine the mechanism of the Ang-(1–7) effect on osmotic water permeability (P
f). P
f was measured in the normal rat IMCD perfused in vitro in presence of agonists [Ang-(1–7), arginine vasopressin (AVP) and Ang-(3–8)], and antagonists of the angiotensin and the vasopressin cascade. Ang-(1–7), but not Ang-(3–8), increased P
f significantly. The effect of Ang-(1–7) on P
f was abolished by its selective antagonist, A-779, added before or after Ang-(1–7). Prostaglandin E2 and the protein kinase A inhibitor H8 also blocked the Ang-(1–7) effect. Blockade of vasopressin V1 receptors by antagonists did not change the Ang-(1–7) effect, but pre-treatment with a V2 antagonist abolished the effect of Ang-(1–7) on P
f. Similarly, pre-treatment with A-779 inhibited AVPs effect on P
f. Forskolin-stimulated P
f was blocked both by A-779 and by the V2 antagonist. Finally, Ang-(1–7) increased cAMP levels in fresh IMCD cell suspensions whilst the forskolin-stimulated cAMP synthesis was decreased by A-779 and the V2 antagonist. These data provide evidence that Ang-(1–7) interacts via its receptor with the AVP V2 system through a mechanism involving adenylate-cyclase activation. 相似文献
85.
Raboni SM Probst CM Bordignon J Zeferino A dos Santos CN 《Journal of medical virology》2005,76(4):553-562
We sequenced the complete S segments of hantaviruses detected from 12 HPS patients living in southern of Brazil. Samples were obtained from patients diagnosed in different years, in distinct areas, and with a broad spectrum of clinical signs. Despite these differences, all the S proteins of hantavirus from Paraná were identical, except for one amino acid substitution. Phylogenetic analyses of the complete S segment nucleotide and amino acid sequences indicated that hantaviruses from Paraná form a distinct clade from those circulating in South and North America. Other hantaviruses from Brazil were not placed in the same clade. The Oligoryzomys nigripes-associated strains ITA37 and ITA38 from Paraguay were found to belong to the same clade as the hantaviruses from Paraná. Paraguay and Paraná state are located at the same latitude and some ecosystems are similar in both places. The geographic position and common rodent hosts could explain this phylogenetic relationship. 相似文献
86.
87.
Connective tissue growth factor expression and Smad signaling during mouse heart development and myocardial infarction. 总被引:5,自引:0,他引:5
Susana M Chuva de Sousa Lopes Alie Feijen Jeroen Korving Olexander Korchynskyi Jonas Larsson Stefan Karlsson Peter ten Dijke Karen M Lyons Roel Goldschmeding Pieter Doevendans Christine L Mummery 《Developmental dynamics》2004,231(3):542-550
Connective tissue growth factor (CTGF) is reported to be a target gene of transforming growth factor beta (TGFbeta) and bone morphogenetic protein (BMP) in vitro. Its physiological role in angiogenesis and skeletogenesis during mouse development has been described recently. Here, we have mapped expression of CTGF mRNA during mouse heart development, postnatal adult life, and after experimental myocardial infarction. Furthermore, we investigated the relationship between CTGF and the BMP/TGFbeta signaling pathway in particular during heart development in mutant mice. Postnatally, CTGF expression in the heart became restricted to the atrium. Strikingly, 1 week after myocardial infarction, when myocytes have disappeared from the infarct zone, CTGF and TGFbeta expression as well as activated forms of TGFbeta but not BMP, Smad effector proteins are colocalized exclusively in the fibroblasts of the scar tissue, suggesting possible cooperation between CTGF and TGFbeta during the pathological fibrotic response. 相似文献
88.
Diversity of genomic breakpoints in TFG-ALK translocations in anaplastic large cell lymphomas: identification of a new TFG-ALK(XL) chimeric gene with transforming activity 总被引:2,自引:0,他引:2
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)
Hernández L Beà S Bellosillo B Pinyol M Falini B Carbone A Ott G Rosenwald A Fernández A Pulford K Mason D Morris SW Santos E Campo E 《The American journal of pathology》2002,160(4):1487-1494
Anaplastic large cell lymphomas are associated with chromosomal aberrations involving the anaplastic lymphoma kinase (ALK) gene at 2p23 that result in the expression of novel chimeric ALK proteins with transforming properties. In most of these tumors, the t(2;5)(p23;q35) generates the NPM-ALK fusion gene. However, several studies have now demonstrated that genes other than NPM may be fused to the ALK gene. We have recently described two different ALK rearrangements involving the TRK-fused gene (TFG) in which the same portion of ALK was fused to different length fragments of the 5' TFG region. These two rearrangements encoded chimeric proteins of 85 kd (TFG-ALK(S)) and 97 kd (TFG-ALK(L)), respectively. In this study, we have identified a new ALK rearrangement in which the catalytic domain of ALK was fused to a larger fragment of the TFG gene (TFG-ALK(XL)), encoding for a fusion protein of 113 kd. Genomic analysis of these three TFG-ALK rearrangements revealed that the TFG breakpoints occur at introns 3, 4, and 5, respectively, whereas the ALK breakpoints always occur in the same intron. No homologous regions or known recombination sequences were found in these regions. Transfection experiments using NIH-3T3 fibroblasts showed a similar transforming efficiency of TFG-ALK variants compared with NPM-ALK. In addition, in common with NPM-ALK, the TFG-ALK proteins formed stable complexes with the signaling proteins Grb2, Shc, and PLC-gamma. In conclusion, these findings indicate that the TFG may use a variety of intronic breakpoints in ALK rearrangements generating fusion proteins of different molecular weights, but with similar transforming potential than NPM-ALK. 相似文献
89.
Survey of rotavirus G and P types associated with human gastroenteritis in São Paulo, Brazil, from 1986 to 1992.
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)
Rotavirus strains causing gastroenteritis in Brazilian children were characterized by PCR-based typing assays. In addition to strains bearing the major human G and P types, large numbers of strains bearing P3 (M37-like), P6 (HCR3-like), untypeable P and G types, and complex mixtures of P and G types not previously recognized were present in the community. 相似文献
90.
Pérez Filgueira DM Mozgovoj M Wigdorovitz A Dus Santos MJ Parreño V Trono K Fernandez FM Carrillo C Babiuk LA Morris TJ Borca MV 《Archives of virology》2004,149(12):2337-2348
Summary. We have previously reported on the use of a tobacco mosaic virus (TMV) vector TMV-30B to express foreign viral antigens for use as experimental immunogens. Here we describe the development of an improved TMV-30B vector that adds a sequence of 7 histidine residues to the C-terminus of recombinant proteins expressed in the vector. We used this TMV-30B-HISc vector to express the VP8* fragment of the VP4 protein from bovine rotavirus (BRV) strain C-486 in plants. Recombinant VP8* protein was purified from N. benthamiana leaves at 7 days post-inoculation by immobilized metal affinity chromatography. The plant-produced VP8* was initially detected using anti-His tag mAb and its antigenic nature was confirmed using both monoclonal and polyclonal specific antisera directed against BRV. Adult female mice, inoculated by the intraperinoteal route with an immunogen containing 4µg of recombinant VP8*, developed a specific and sustained response to the native VP8* from the homologous BRV. Eighty five percent of suckling mice from immunized dams that were challenged with the homologous virus at the fifth day of age were protected from virus as compared to 35% of the pups from mothers immunized with a control protein. These results demonstrate that the plant-produced VP8* was able to induce passive protection in the new born through the immunization of dams. This suggests that the technology presented here provides a simple method for using plants as an inexpensive alternative source for production of recombinant anti-rotavirus antigens.Authors contributed equally to the results presented in this report. 相似文献