全文获取类型
收费全文 | 8374篇 |
免费 | 542篇 |
国内免费 | 58篇 |
专业分类
耳鼻咽喉 | 42篇 |
儿科学 | 201篇 |
妇产科学 | 225篇 |
基础医学 | 1308篇 |
口腔科学 | 51篇 |
临床医学 | 792篇 |
内科学 | 2019篇 |
皮肤病学 | 145篇 |
神经病学 | 810篇 |
特种医学 | 249篇 |
外科学 | 1486篇 |
综合类 | 39篇 |
一般理论 | 3篇 |
预防医学 | 524篇 |
眼科学 | 89篇 |
药学 | 453篇 |
中国医学 | 7篇 |
肿瘤学 | 531篇 |
出版年
2023年 | 43篇 |
2022年 | 79篇 |
2021年 | 171篇 |
2020年 | 111篇 |
2019年 | 167篇 |
2018年 | 213篇 |
2017年 | 150篇 |
2016年 | 151篇 |
2015年 | 200篇 |
2014年 | 292篇 |
2013年 | 396篇 |
2012年 | 582篇 |
2011年 | 596篇 |
2010年 | 379篇 |
2009年 | 340篇 |
2008年 | 547篇 |
2007年 | 577篇 |
2006年 | 573篇 |
2005年 | 546篇 |
2004年 | 575篇 |
2003年 | 552篇 |
2002年 | 581篇 |
2001年 | 45篇 |
2000年 | 62篇 |
1999年 | 74篇 |
1998年 | 124篇 |
1997年 | 97篇 |
1996年 | 88篇 |
1995年 | 75篇 |
1994年 | 67篇 |
1993年 | 56篇 |
1992年 | 45篇 |
1991年 | 28篇 |
1990年 | 27篇 |
1989年 | 32篇 |
1988年 | 20篇 |
1987年 | 31篇 |
1986年 | 28篇 |
1985年 | 22篇 |
1984年 | 29篇 |
1983年 | 22篇 |
1982年 | 31篇 |
1981年 | 32篇 |
1980年 | 15篇 |
1979年 | 11篇 |
1978年 | 13篇 |
1977年 | 10篇 |
1976年 | 11篇 |
1975年 | 8篇 |
1974年 | 9篇 |
排序方式: 共有8974条查询结果,搜索用时 31 毫秒
81.
Algros MP Collonge-Rame MA Bedgejian I Tropet Y Delattre O Kantelip B 《Annales de pathologie》2003,23(3):244-248
Extraskeletal myxoid chondrosarcoma (EMC) is a phenotypically and genotypically distinct entity with a protracted course. A documented case of an extraskeletal myxoid chondrosarcoma characterized by a t(9; 17) (q22; q11) translocation with a neuroendocrine and neural differentiation is reported. 相似文献
82.
83.
Quigley CA Tan JA He B Zhou ZX Mebarki F Morel Y Forest MG Chatelain P Ritzén EM French FS Wilson EM 《Mechanisms of ageing and development》2004,125(10-11):683-695
Partial androgen insensitivity with sex phenotype variation in two unrelated families was associated with missense mutations in the androgen receptor (AR) gene that disrupted the AR NH(2)-terminal/carboxy terminal interaction. Each mutation caused a single amino acid change within the region of the ligand-binding domain that forms activation function 2 (AF2). In one family, the mutation I737T was in alpha helix 4 and in the other F725L was between helices 3 and 4. Neither mutation altered androgen binding as determined by assays of mutant AR in the patient's cultured genital skin fibroblasts or of recombinant mutant receptors transfected into COS cells. In transient cotransfection assays in CV1 cells, transactivation with the AR mutants at low concentrations of DHT was reduced several fold compared with wild-type AR but increased at higher concentrations. Defects in NH(2)-terminal/carboxy terminal interactions were identified in mammalian two hybrid assays. In similar assays, there was reduced binding of the p160 coactivators TIF2/SRC2 and SRC1 to the mutant AR ligand binding domains (LBD). In the family with AR I737T, sex phenotype varied from severely defective masculinization in the proband to a maternal great uncle whose only manifestation of AIS was severe gynecomastia. He was fertile and passed the mutation to two daughters. The proband of the F725L family was also incompletely masculinized but was raised as a male while his half-sibling by a different father was affected more severely and reared as a female. These studies indicate that the function of an AR AF2 mutant in male development can vary greatly depending on the genetic background. 相似文献
84.
Bernard Boutevin Yves Pitrasanta Mohamed Taha Tarek El Sarraf 《Macromolecular chemistry and physics.》1983,184(12):2401-2407
New macromers 4, 8, and 10, containing ester, alcohol, or acid functions, were prepared starting with vinyl chloride (CV) or vinylidene dichloride (CV2). The telomer 1, resulting from CV2 and CCI4 was telomerized with allyl acetate and the product was transformed into the acrylate 4 by hydrolysis of the reaction product and subsequent esterification. Macromers 8 and 10 were prepared from CV by radical telomerization with thioglycolic acid (7) and 2-mercaptoethanol (9), respectively. Reactive double bonds were introduced into these macromers by reaction with acrylic acid, Vinyl chloroformate, methacryloyl chloride, or 2,3 -epoxypropyle methacrylate, leading to new macromers 12, 13, 14, and 15, respectively. 相似文献
85.
Ouadrhiri Y Pilette C Monteiro RC Vaerman JP Sibille Y 《American journal of respiratory cell and molecular biology》2002,26(3):315-332
Human alveolar macrophages (HAM) express FcalphaR receptors for immunoglobulin (Ig)A which could link humoral and cellular branches of lung immunity. Here, we investigate the effects of polymeric (p-IgA) and secretory (S-IgA) IgA interaction with Fc(alpha)R on lipopolysaccharide (LPS)- and phorbol myristate acetate (PMA)-activated respiratory burst and TNF-alpha release by HAM. Activation of HAM with LPS and PMA increases the respiratory burst and TNF-alpha release through activation of the extracellular signal-related protein kinases 1 and 2 (ERK1/2) pathway, because these effects are inhibited by treatment of HAM with PD98059, a selective inhibitor of mitogen-activated protein (MAP)/ERK kinases (MEK) pathway. S-IgA and p-IgA downregulate the LPS-increased respiratory burst in HAM through an inhibition of ERK1/2 activity. In contrast, p- and S-IgA induce an increase in the respiratory burst of PMA-treated HAM. This effect is associated with an upregulation by IgA of the PMA-induced phosphorylation of ERK1/2 and is also inhibited by PD98059. Moreover, p-IgA and S-IgA enhance TNF-alpha release by HAM through an alternative pathway distinct from ERK1/2. Because LPS is known to activate nuclear factor-kappaB (NF-kappaB) in HAM, we evaluate the effect of IgA on NF-kappaB. Treatment of HAM with LPS, p- and S-IgA, but not PMA, induces NF-kappaB activation through IkappaBalpha phosphorylation and subsequent proteolysis. Antioxidants, namely N-acetylcysteine (NAC) and glutathione (GSH), have no effects on IgA-mediated NF-kappaB nuclear translocation and only a minor and late effect on that of LPS, suggesting that reactive oxygen intermediates (ROI) play a minor role in HAM activation through NF-kappaB. TNF-alpha release by LPS-activated HAM is sensitive to NF-kappaB inhibition and only partly to oxidant scavenging. In contrast, TNF-alpha release by IgA-treated HAM is not dependent on oxidants and only partly dependent on NF-kappaB. Our results show a differential HAM regulation by IgA through both dependent and independent modulation of ERK pathway. In addition, IgA activates NF-kappaB and this effect was independent on oxidants. These data may help to understand the role of IgA in both lung protection and inflammation. 相似文献
86.
Baris O Delettre C Amati-Bonneau P Surget MO Charlin JF Catier A Derieux L Guyomard JL Dollfus H Jonveaux P Ayuso C Maumenee I Lorenz B Mohammed S Tourmen Y Bonneau D Malthièry Y Hamel C Reynier P 《Human mutation》2003,21(6):656-656
The OPA1 gene, encoding a dynamin-related GTPase that plays a role in mitochondrial biogenesis, is implicated in most cases of autosomal dominant optic atrophy (ADOA). Sixty-nine pathogenic OPA1 mutations have been reported so far. Most of these are truncating mutations located in the GTPase domain coding region (exons 8-16) and at the 3'-end (exons 27-28). We screened 44 patients with typical ADOA using PCR-sequencing. We also tested 20 sporadic cases of bilateral optic atrophy compatible with ADOA. Of the 18 OPA1 mutations found, 14 have never been previously reported. The novel mutations include one nonsense mutation, 3 missense mutations, 6 deletions, one insertion and 3 exon-skipping mutations. Two of these are de novo mutations, which were found in 2 patients with sporadic optic atrophy. The recurrent c.2708_2711delTTAG mutation was found in 2 patients with a severe congenital presentation of the disease. These results suggest that screening for OPA1 gene mutations may be useful for patients with optic atrophy who have no affected relatives, or when the presentation of the disease is atypical as in the case of early onset optic atrophy. 相似文献
87.
Septins: a ring to part mother and daughter 总被引:15,自引:0,他引:15
The septins are well conserved GTPases found in animals and fungi. In yeast, they are required for the formation of 10-nm filaments, with which they co-localize at the bud neck. Therefore, septins have been proposed to be components of the neck filaments and to have polymerization properties. In support of this hypothesis, septin complexes purified from yeast and flies form filaments in vitro. However, recent studies have questioned the relevance of septin filament formation for septin function. Particularly, septin polymerization may not be required for their function in cytokinesis. New septin functions have also been recently uncovered: in budding yeast, the septin ring is required for the maintenance of cell polarity. It forms a cortical barrier that prevents lateral diffusion of membrane-associated proteins through the bud neck. Here, we review the most recent functional and biochemical data, to discuss whether there is a link between septin polymerization properties and septin function. 相似文献
88.
Genetic polymorphism of cytomegalovirus strains responsible of congenital infections 总被引:1,自引:0,他引:1
Picone O Costa JM Ville Y Chaix ML Rouzioux C Leruez-Ville M 《Pathologie-biologie》2004,52(9):534-539
OBJECTIVES: Congenital Cytomegalovirus (CMV) infection is the main cause of neurological handicap in young children. The objective for studying genetic polymorphism of strains responsible for congenital infection is to identify CMV strains or groups of strains which would be more frequent in this context and/or which would be responsible for more severe congenital infection. METHODS: In this paper, we report and analyze the literature concerning the genetic polymorphism of CMV strains responsible of congenital infection, in the genes coding for the envelop protein B and the non structural UL144 protein and in the CMV short tandem repeats. RESULTS AND CONCLUSION: All UL144 and gB genotypes can be vertically transmitted from mothers to fetuses, none of these studies has shown any link between the genotypes and the severity of congenital disease. Moreover, no link between short tandem repeats polymorphism and severity of congenital disease has been demonstrated. However, short tandem repeats analysis may be a powerful tool to study the epidemiology of CMV congenital infections. 相似文献
89.
Alain Verloes Yves Gillerot Jean-Paul Langhendries Jean-Pierre Fryns Lucien Koulischer 《American journal of medical genetics. Part A》1992,43(4):669-677
We report on a case of neonatal hypothalamic hamartoblastoma with holoprosencephaly, Hirschsprung disease, and tetramelic postaxial polydactyly. Twenty-seven previous cases of congenital hypothalamic embryonic tumours with associated congenital defects are reviewed. A classification in isolated, associated, and syndromal forms is proposed. The difficulties encountered in differential diagnosis between the syndromal form (mainly represented by the Pallister-Hall syndrome) and related diseases as Smith-Lemli-Opitz type II, holoprosencephaly-polydactyly, orofaciodigital type VI and hydrolethalus syndromes are outlined. Two pathogenic mechanisms are discussed: a classical pleiotropic model and single sequence model. The latter is sufficient to delineate syndromal hypothalamic hamartoblastoma. With the former, syndromal hypothalamic hamartoblastoma cannot be clearly recognized in the absence of a CNS tumour, a child with syndromal hypothalamic hamartoblastoma cannot be reliably diagnosed as Pallister-Hall rather than another MCA syndrome, and, ultimately, the existence of Pallister-Hall syndrome could be questioned, as it could only be the extreme expression of one or several other syndromes. As this hypothesis cannot be proven or disproven at this point, the authors suggest creating the concept of multiplex phenotype. “Cerebro-Acro-Visceral Early lethality multiplex syndrome” is suggested to encompass all the ambiguous cases. Within this complex, an operative classification key is proposed. © 1992 Wiley-Liss, Inc. 相似文献
90.
Vincent Guion Philipe De Souto Barreto Yves Rolland 《Journal of the American Medical Directors Association》2021,22(2):393-398.e3
ObjectiveTo describe nursing home residents’ (NHRs) functional trajectories and mortality after a transfer to the emergency department (ED).DesignCase-control observational multicenter study.Setting and ParticipantsIn total, 1037 NHRs presenting to 17 EDs in France over 4 nonconsecutive weeks in 2016.MethodsFinite mixture models were fitted to longitudinal data on activities of daily living (ADL) scores before transfer (time 1), during hospitalization (time 2), and within 1 week after discharge (time 3) to identify groups of NHRs following similar functional evolution. Factors associated with mortality were investigated by Cox regressions.ResultsTrajectory modeling identified 4 distinct trajectories of ADL. The first showed a high and stable (across time 1, time 2, and time 3) functional capacity around 5.2/6 ADL points, with breathlessness as the main condition leading to transfer. The second displayed an initial 37.8% decrease in baseline ADL performance (between time 1 and time 2), followed by a 12.5% recovery of baseline ADL performance (time 2?time 3), with fractures as the main condition. The third displayed a similar initial decrease, followed by a 6.7% recovery. The fourth displayed an initial 70.1% decrease, followed by an 8.5% recover, with more complex geriatric polypathology situations. Functional decline was more likely after being transferred for a cerebrovascular condition or for a fracture, after being discharged from ED to a surgery department, and with a heavier burden of distressing symptoms during transfer. Mortality after ED transfer was more likely in older NHRs, those in a more severe condition, those who were hospitalized more frequently in the past month, and those transferred for cerebrovascular conditions or breathlessness.Conclusions and ImplicationsIdentified trajectories and factors associated with functional decline and mortality should help clinicians decide whether to transfer NHRs to ED. NHRs with high functional ability seem to benefit from ED transfers whereas on-site alternatives should be sought for those with poor functional ability. 相似文献