全文获取类型
收费全文 | 2626篇 |
免费 | 252篇 |
国内免费 | 15篇 |
专业分类
耳鼻咽喉 | 24篇 |
儿科学 | 116篇 |
妇产科学 | 41篇 |
基础医学 | 329篇 |
口腔科学 | 68篇 |
临床医学 | 313篇 |
内科学 | 462篇 |
皮肤病学 | 29篇 |
神经病学 | 200篇 |
特种医学 | 203篇 |
外国民族医学 | 1篇 |
外科学 | 413篇 |
综合类 | 131篇 |
一般理论 | 1篇 |
预防医学 | 220篇 |
眼科学 | 41篇 |
药学 | 192篇 |
中国医学 | 1篇 |
肿瘤学 | 108篇 |
出版年
2022年 | 16篇 |
2021年 | 41篇 |
2020年 | 24篇 |
2019年 | 39篇 |
2018年 | 59篇 |
2017年 | 47篇 |
2016年 | 46篇 |
2015年 | 46篇 |
2014年 | 65篇 |
2013年 | 107篇 |
2012年 | 115篇 |
2011年 | 109篇 |
2010年 | 109篇 |
2009年 | 84篇 |
2008年 | 93篇 |
2007年 | 106篇 |
2006年 | 97篇 |
2005年 | 95篇 |
2004年 | 85篇 |
2003年 | 85篇 |
2002年 | 54篇 |
2001年 | 62篇 |
2000年 | 88篇 |
1999年 | 61篇 |
1998年 | 64篇 |
1997年 | 64篇 |
1996年 | 67篇 |
1995年 | 59篇 |
1994年 | 37篇 |
1993年 | 49篇 |
1992年 | 49篇 |
1991年 | 73篇 |
1990年 | 58篇 |
1989年 | 60篇 |
1988年 | 57篇 |
1987年 | 50篇 |
1986年 | 55篇 |
1985年 | 40篇 |
1984年 | 40篇 |
1983年 | 34篇 |
1982年 | 21篇 |
1981年 | 27篇 |
1980年 | 20篇 |
1979年 | 18篇 |
1978年 | 18篇 |
1977年 | 16篇 |
1976年 | 19篇 |
1975年 | 20篇 |
1972年 | 17篇 |
1968年 | 14篇 |
排序方式: 共有2893条查询结果,搜索用时 15 毫秒
21.
Mutations in the retinal guanylate cyclase (RETGC-1) gene in dominant cone-rod dystrophy 总被引:3,自引:0,他引:3
Kelsell RE; Gregory-Evans K; Payne AM; Perrault I; Kaplan J; Yang RB; Garbers DL; Bird AC; Moore AT; Hunt DM 《Human molecular genetics》1998,7(7):1179-1184
The dominant cone-rod dystrophy gene CORD6 has previously been mapped to
within an 8 cM interval on chromosome 17p12-p13. The retinal- specific
guanylate cyclase gene (RETGC-1), which maps to within this genetic
interval and previously was implicated in Leber's congenital amaurosis, was
screened for mutations within this family and in a panel of small families
and individuals with various cone and cone- rod dystrophy phenotypes. A
missense mutation (E837D) was identified in affected members of the CORD6
family, as well as a second missense mutation (R838C) in three other
families with dominant cone-rod dystrophy. RETGC-1 is only the fourth gene
to be implicated in cone-rod dystrophy and this is the first report of
dominant mutations in this gene.
相似文献
22.
Van de Velde H; De Vos A; Joris H; Nagy ZP; Van Steirteghem AC 《Human reproduction (Oxford, England)》1998,13(11):3160-3164
In human in-vitro fertilization (IVF), the oocytes are surrounded by
cumulus and corona cells at the time of insemination so that their maturity
cannot easily be evaluated. The best IVF results are obtained if the
oocytes are inseminated 2-6 h after retrieval. In the intracytoplasmic
sperm injection (ICSI) procedure, the oocytes are denuded by enzymatic and
mechanical treatment in order to be able to perform the injection. As a
consequence, the nuclear maturity of the oocytes can be evaluated and only
those that have extruded the first polar body are injected. However,
metaphase-II oocytes that have not yet reached cytoplasmic maturity cannot
be recognized. The purpose of this study was to investigate the effect of
different timing of cumulus- corona cell removal and injection on the
outcome of ICSI. For this we allowed the oocytes to complete in-vitro
cytoplasmic maturation in two different culture conditions: (i) surrounded
by their cumulus and corona cells or (ii) totally denuded. We performed
three different studies on sibling oocytes obtained after a standardized
buserelin/human menopausal gonadotrophin (HMG) protocol. We investigated
the effect of early (1-2 h after retrieval) and late (5-6 h after
retrieval) oocyte denudation and injection on the survival and
fertilization of the injected oocytes and on embryo cleavage after
fertilization. We found no statistically significant differences between
early and late injection, indicating that after a standardized
buserelin/HMG protocol the metaphase-II oocytes do not need time for
further cytoplasmic maturation. Furthermore, a different timing of
cumulus-corona cell removal has no effect on the outcome of ICSI,
suggesting that the surrounding cells are not necessary for survival,
fertilization and cleavage after ICSI.
相似文献
23.
Novero V; Camus M; Tournaye H; Smitz J; Verheyen G; Joris H; Derde MP; Van Steirteghem AC; Devroey P 《Human reproduction (Oxford, England)》1997,12(1):59-63
Serum follicle stimulating hormone (FSH) is routinely measured when
evaluating the infertile male for intracytoplasmic sperm injection (ICSI).
However, among the sperm parameters, only its relationship with sperm
concentration is well documented. Few investigations concern the
relationship between FSH and sperm motility and morphology, and the results
of ICSI. A retrospective study of 316 couples who underwent ICSI was
carried out to determine the relationships between serum FSH concentrations
in the male and (i) standard sperm parameters_(concentration, motility and
morphology) and (ii) fertilization, cleavage, pregnancy and implantation
rates after ICSI. There was an inverse correlation with sperm concentration
and total motility but no relationship was found with progressive motility
and sperm morphology. Neither was any relationship found between serum FSH
and fertilization, cleavage, pregnancy and implantation rates, and the
results of ICSI. These findings suggest the need to review the routine
measurement of serum FSH in the infertile male when ICSI is the planned
treatment procedure.
相似文献
24.
Decorin inhibition of PDGF-stimulated vascular smooth muscle cell function: potential mechanism for inhibition of intimal hyperplasia after balloon angioplasty 下载免费PDF全文
Nili N Cheema AN Giordano FJ Barolet AW Babaei S Hickey R Eskandarian MR Smeets M Butany J Pasterkamp G Strauss BH 《The American journal of pathology》2003,163(3):869-878
Decorin is a small proteoglycan that binds to transforming growth factor-beta (TGF-beta) and inhibits its activity. However, its interaction with platelet-derived growth factor (PDGF), involved in arterial repair after injury, is not well characterized. The objectives of this study were to assess decorin-PDGF and decorin-PDGF receptor (PDGFR) interactions, the in vitro effects of decorin on PDGF-stimulated smooth muscle cell (SMC) functions and the in vivo effects of decorin overexpression on arterial repair in a rabbit carotid balloon-injury model. Decorin binding to PDGF was demonstrated by solid-phase binding and affinity cross-linking assays. Decorin potently inhibited PDGF-stimulated PDGFR phosphorylation. Pretreatment of rabbit aortic SMC with decorin significantly inhibited PDGF-stimulated cell migration, proliferation, and collagen synthesis. Decorin overexpression by adenoviral-mediated gene transfection in balloon-injured carotid arteries significantly decreased intimal cross-sectional area and collagen content by approximately 50% at 10 weeks compared to beta-galactosidase-transfected or balloon-injured, non-transfected controls. This study shows that decorin binds to PDGF and inhibits its stimulatory activity on SMCs by preventing PDGFR phosphorylation. Decorin overexpression reduces intimal hyperplasia and collagen content after arterial injury. Decorin may be an effective therapy for the prevention of intimal hyperplasia after balloon angioplasty. 相似文献
25.
Phase Variation of Campylobacter jejuni 81-176 Lipooligosaccharide Affects Ganglioside Mimicry and Invasiveness In Vitro 总被引:4,自引:0,他引:4 下载免费PDF全文
Patricia Guerry Christine M. Szymanski Martina M. Prendergast Thomas E. Hickey Cheryl P. Ewing Dawn L. Pattarini Anthony P. Moran 《Infection and immunity》2002,70(2):787-793
The outer cores of the lipooligosaccharides (LOS) of many strains of Campylobacter jejuni mimic human gangliosides in structure. A population of cells of C. jejuni strain 81-176 produced a mixture of LOS cores which consisted primarily of structures mimicking GM(2) and GM(3) gangliosides, with minor amounts of structures mimicking GD(1b) and GD(2). Genetic analyses of genes involved in the biosynthesis of the outer core of C. jejuni 81-176 revealed the presence of a homopolymeric tract of G residues within a gene encoding CgtA, an N-acetylgalactosaminyltransferase. Variation in the number of G residues within cgtA affected the length of the open reading frame, and these changes in cgtA corresponded to a change in LOS structure from GM(2) to GM(3) ganglioside mimicry. Site-specific mutation of cgtA in 81-176 resulted in a major LOS core structure that lacked GalNAc and resembled GM(3) ganglioside. Compared to wild-type 81-176, the cgtA mutant showed a significant increase in invasion of INT407 cells. In comparison, a site-specific mutation of the neuC1 gene resulted in the loss of sialic acid in the LOS core and reduced resistance to normal human serum but had no affect on invasion of INT407 cells. 相似文献
26.
Autoimmune pancreatitis (AIP), a recently defined disease of unknown etiology, is characterized by inflammatory infiltrates in the pancreas with conspicuous involvement of the ducts. The disease clinically manifests in humans as epigastric pain, weight loss, and jaundice. This report describes the development of a novel animal model of this disease in the rat, which we have termed experimental autoimmune pancreatitis. Adoptive transfer of amylase-specific CD4(+) T cells was able to confer pancreatitis to naive syngeneic recipient animals. No treatments before the adoptive transfer of T cells were necessary for disease to ensue, and the severity of disease was proportional to the number of T cells administered. The pancreatic lesions of rats with experimental autoimmune pancreatitis were characterized histologically as overwhelmingly lymphocytic with occasional plasma cells, neutrophils, and mast cells. Acinar tissue destruction and ductular inflammation were common features, with less frequent involvement of larger ducts. Immunohistochemical analysis revealed the presence of CD4(+) T cells in large numbers as well as CD8(+) T cells, macrophages, and dendritic cells. Expression of MHC I and MHC II also increased at the site of the lesion. Clinically, the disease manifested as either failure to gain weight at a rate concomitant with control animals or as outright weight loss. Thus, administration of activated CD4(+) T cells specific for the pancreatic enzyme amylase can induce pancreatitis in the rat in a manner that is reminiscent of human AIP. 相似文献
27.
The GAP-related domain of tuberin, the product of the TSC2 gene, is a target for missense mutations in tuberous sclerosis 总被引:5,自引:0,他引:5
Maheshwar MM; Cheadle JP; Jones AC; Myring J; Fryer AE; Harris PC; Sampson JR 《Human molecular genetics》1997,6(11):1991-1996
Tuberous sclerosis is an autosomal dominant trait in which the
dysregulation of cellular proliferation and differentiation results in the
development of hamartomatous growths in many organs. The TSC2 gene is one
of two genes determining tuberous sclerosis. Inactivating germline
mutations of TSC2 in patients with tuberous sclerosis and somatic loss of
heterozygosity at the TSC2 locus in the associated hamartomas indicate that
TSC2 functions as a tumour suppressor gene and that loss of function is
critical to expression of the tuberous sclerosis phenotype. The TSC2
product, tuberin, has a region of homology with the GTPase activating
protein rap1GAP and stimulates the GTPase activity of rap1a and rab5a in
vitro. Here we show that the region of homology between tuberin and human
rap1GAP and the murine GAP mSpa1 is more extensive than previously reported
and spans approximately 160 amino acid residues encoded within exons 34-38
of the TSC2 gene. Single strand conformation polymorphism analysis of these
exons in 173 unrelated patients with tuberous sclerosis and direct
sequencing of variant conformers together with study of additional family
members enabled characterisation of disease associated mutations in 14
cases. Missense mutations, which occurred in exons 36, 37 and 38 were
identified in eight cases, four of whom shared the same recurrent change
P1675L. Each of the five different missense mutations identified was shown
to occur de novo in at least one sporadic case of tuberous sclerosis. The
high proportion of missense mutations detected in the region of the TSC2
gene encoding the GAP-related domain supports its key role in the
regulation of cellular growth.
相似文献
28.
Marjolijn Bornebroek Joost Haan Marion LC Maat-Schieman Sjoerd G Van Duinen Raymund AC Roos 《Brain pathology (Zurich, Switzerland)》1996,6(2):111-114
Hereditary cerebral hemorrhage with amyloidosis - Dutch type (HCHWA-D) is an autosomal dominant disease caused by deposition of β-amyloid in the leptomeningeal arteries and cortical arterioles, in addition to preamyloid deposits and amyloid plaques in the brain parenchyma.
The disease is due to a point mutation at codon 693 of the amyloid precursor protein (βPP) gene at chromosome 21. Since this point mutation is diagnostic for HCHWA-D, presymptomatic testing is feasible and offered, together with genetic counselling and psychological support, to subjects at risk. HCHWA-D is clinically characterized by recurrent strokes, in addition to dementia, which can occur after the first stroke but also preceding it. Radiological studies revealed focal lesions (hemorrhages, hemorrhagic and non-hemorrhagic infarctions) and diffuse white matter damage. Diffuse white matter hyperintensities on MRI are an early symptom of HCHWA-D since they have been found on MRI scans of subjects who had not suffered a stroke.
The presence of the diagnostic point mutation makes HCHWA-D a useful model to study the effects of cerebral amyloid angiopathy in vivo. The characteristic pathological abnormalities and its implications for Alzheimer's disease will be discussed in Part II of this article 相似文献
The disease is due to a point mutation at codon 693 of the amyloid precursor protein (βPP) gene at chromosome 21. Since this point mutation is diagnostic for HCHWA-D, presymptomatic testing is feasible and offered, together with genetic counselling and psychological support, to subjects at risk. HCHWA-D is clinically characterized by recurrent strokes, in addition to dementia, which can occur after the first stroke but also preceding it. Radiological studies revealed focal lesions (hemorrhages, hemorrhagic and non-hemorrhagic infarctions) and diffuse white matter damage. Diffuse white matter hyperintensities on MRI are an early symptom of HCHWA-D since they have been found on MRI scans of subjects who had not suffered a stroke.
The presence of the diagnostic point mutation makes HCHWA-D a useful model to study the effects of cerebral amyloid angiopathy in vivo. The characteristic pathological abnormalities and its implications for Alzheimer's disease will be discussed in Part II of this article 相似文献
29.
Variations of the origin of the artery of the sinoatrial node in normal human hearts 总被引:8,自引:0,他引:8
Summary The artery of the sino-atrial node was studied in 100 normal human hearts after injection of each coronary artery with coloured gelatine containing a radiopaque substance. The hearts belonged to 69 males and 31 females, being 64 Caucasians and 36 non-Caucasians (Negroes and Mulattoes) whose age ranged from 7 to 80 years. Since the individuals had committed suicide or were victims of accidents, their hearts, after pathologists' evaluation, were considered normal. The sinoatrial node of the normal human heart is supplied by the right coronary artery more frequently (58%±4.9% of the cases) than by the left (42%±4.9). The right anterior medial atrial artery, originating from the right coronary at the level of the medial third of the right anterior quadrant of the atrial dome, is most frequently (50%±5) responsible for the blood supply of the sinoatrial node. Among the branches of the left coronary artery, the left anterior medial atrial artery, originating at the level of the medial third of the left. anterior quadrant of the atrial cupola, was the most frequent blood supplier (25%±4.3) of the sinoatrial node. The origin of the artery of the sinoatrial node from the proximal portion or trunk of the left coronary artery was less frequent (12%±3.2) than the origin from the circumflex artery (30%±4.5). Neither sex nor race influenced the variations of the origin of the sino-atrial node.
Variations d'origine de l'artère du noeud sinu-atrial du coeur humain normal
Résumé L'a. du noeud sinu-atrial a été étudiée sur 100 coeurs humains normaux après injection de chaque a. coronaire à la gélatine colorée additionnée d'une substance radio-opaque. Les coeurs provenaient de 69 hommes et 31 femmes, 64 caucasiens et 36 non caucasiens (nègres et mulâtres) âgés de 7 à 80 ans. Ces sujets étant décédés par suicide ou des suites d'accidents, leurs coeurs ont été considérés comme normaux après examen anatomo-pathologique. Le noeud sinu-atrial du coeur humain est vascularisé par l'a. coronaire droite plus fréquemment (58 %±4,9) que par l'a. coronaire gauche (42 %±4). L'a. atriale antéro-médiale droite, issue de l'a. coronaire droite au niveau du tiers médial du quadrant antérieur droit du dôme atrial est l'artère la plus fréquemment en cause (50 %±5) dans la vascularisation du noeud sinuatrial. Parmi les branches de l'a. coronaire gauche, l'a. atriale antéro-médiale gauche, née au niveau du tiers médial du quadrant antérieur gauche du dôme atrial, était la branche la plus fréquemment en cause (25 %±4,3) dans la vascularisation du noeud sinu-atrial. La naissance de l'a. du noeud sinu-atrial à partir de la partie proximale ou du tronc de l'a. coronaire gauche était moins fréquente (12 %±3,2) que son origine à partir du rameau circonflexe (30 %±4,5). Les variations d'origine de l'a. du noeud sinu-atrial n'apparaissaient pas influencées par le sexe ou la race.相似文献
30.
Cervical smear results reporting the presence of inflammation are regularly encountered by smeartakers, yet the significance of this finding is not clear. We wished to evaluate whether the presence of inflammation on smear test was associated with a higher incidence of lower genital tract infection. A retrospective review was carried out on women attending our colposcopy unit for their first visit during 2001. Results of 256 women were available for analysis. Evidence of inflammation was found in 9.7% of smears. Genital tract infection was found in 29.2% of women overall. Infection with more than one micro-organism was present in 8.9 percent. Forty eight percent of women having inflammatory changes on smear test had genital tract infection. This compared with 27.3% of women whose smear tests showed no evidence of inflammation. Prevalence of infection with Chlamydia trachomatis, Candida, Bacteroides and Gardnerella vaginalis was higher in the inflammatory smear group. This study shows that women with an inflammatory smear are more likely to harbour genital tract infection than women whose smear shows no evidence of inflammation. Chlamydia infection in particular has long-term fertility consequences through its potential to cause asymptomatic tubal damage: it was present in a substantial proportion of women with inflammation on smear (20%). Screening for lower genital tract infection via high vaginal swab and either intracervical swab or urinary screening for Chlamydia infection should be carried out in all women with smear tests reporting the presence of inflammation. 相似文献