全文获取类型
收费全文 | 5187篇 |
免费 | 366篇 |
国内免费 | 22篇 |
专业分类
耳鼻咽喉 | 30篇 |
儿科学 | 56篇 |
妇产科学 | 50篇 |
基础医学 | 773篇 |
口腔科学 | 40篇 |
临床医学 | 592篇 |
内科学 | 1140篇 |
皮肤病学 | 84篇 |
神经病学 | 772篇 |
特种医学 | 313篇 |
外科学 | 753篇 |
综合类 | 14篇 |
预防医学 | 222篇 |
眼科学 | 40篇 |
药学 | 297篇 |
中国医学 | 6篇 |
肿瘤学 | 393篇 |
出版年
2023年 | 61篇 |
2022年 | 129篇 |
2021年 | 279篇 |
2020年 | 150篇 |
2019年 | 239篇 |
2018年 | 253篇 |
2017年 | 175篇 |
2016年 | 175篇 |
2015年 | 212篇 |
2014年 | 249篇 |
2013年 | 316篇 |
2012年 | 494篇 |
2011年 | 474篇 |
2010年 | 253篇 |
2009年 | 220篇 |
2008年 | 277篇 |
2007年 | 252篇 |
2006年 | 241篇 |
2005年 | 204篇 |
2004年 | 171篇 |
2003年 | 117篇 |
2002年 | 94篇 |
2001年 | 36篇 |
2000年 | 34篇 |
1999年 | 29篇 |
1998年 | 23篇 |
1997年 | 13篇 |
1996年 | 16篇 |
1995年 | 19篇 |
1994年 | 12篇 |
1993年 | 12篇 |
1992年 | 29篇 |
1991年 | 24篇 |
1990年 | 29篇 |
1989年 | 31篇 |
1988年 | 26篇 |
1987年 | 22篇 |
1986年 | 15篇 |
1985年 | 15篇 |
1984年 | 12篇 |
1983年 | 14篇 |
1982年 | 7篇 |
1981年 | 10篇 |
1980年 | 9篇 |
1979年 | 13篇 |
1977年 | 10篇 |
1975年 | 9篇 |
1974年 | 14篇 |
1973年 | 9篇 |
1972年 | 8篇 |
排序方式: 共有5575条查询结果,搜索用时 125 毫秒
11.
Albertine Dubois Julien Dauguet Anne-Sophie Herard Laurent Besret Edouard Duchesnay Vincent Frouin Philippe Hantraye Gilles Bonvento Thierry Delzescaux 《Journal of cerebral blood flow and metabolism》2007,27(10):1742-1755
Besides the newly developed positron emission tomography scanners (microPET) dedicated to the in vivo functional study of small animals, autoradiography remains the reference technique widely used for functional brain imaging and the gold standard for the validation of in vivo results. The analysis of autoradiographic data is classically achieved in two dimensions (2D) using a section-by-section approach, is often limited to few sections and the delineation of the regions of interest to be analysed is directly performed on autoradiographic sections. In addition, such approach of analysis does not accommodate the possible anatomical shifts linked to dissymmetry associated with the sectioning process. This classic analysis is time-consuming, operator-dependent and can therefore lead to non-objective and non-reproducible results. In this paper, we have developed an automated and generic toolbox for processing of autoradiographic and corresponding histological rat brain sections based on a three-step approach, which involves: (1) an optimized digitization dealing with hundreds of autoradiographic and histological sections; (2) a robust reconstruction of the volumes based on a reliable registration method; and (3) an original 3D-geometry-based approach to analysis of anatomical and functional post-mortem data. The integration of the toolbox under a unified environment (in-house software BrainVISA, http://brainvisa.info) with a graphic interface enabled a robust and operator-independent exploitation of the overall anatomical and functional information. We illustrated the substantial qualitative and quantitative benefits obtained by applying our methodology to an activation study (rats, n=5, under unilateral visual stimulation). 相似文献
12.
Besle J Fort A Giard MH 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2005,166(3-4):337-344
The mismatch negativity (MMN) component of auditory event-related brain potentials can be used as a probe to study the representation of sounds in auditory sensory memory (ASM). Yet it has been shown that an auditory MMN can also be elicited by an illusory auditory deviance induced by visual changes. This suggests that some visual information may be encoded in ASM and is accessible to the auditory MMN process. It is not known, however, whether visual information affects ASM representation for any audiovisual event or whether this phenomenon is limited to specific domains in which strong audiovisual illusions occur. To highlight this issue, we have compared the topographies of MMNs elicited by non-speech audiovisual stimuli deviating from audiovisual standards on the visual, the auditory, or both dimensions. Contrary to what occurs with audiovisual illusions, each unimodal deviant elicited sensory-specific MMNs, and the MMN to audiovisual deviants included both sensory components. The visual MMN was, however, different from a genuine visual MMN obtained in a visual-only control oddball paradigm, suggesting that auditory and visual information interacts before the MMN process occurs. Furthermore, the MMN to audiovisual deviants was significantly different from the sum of the two sensory-specific MMNs, showing that the processes of visual and auditory change detection are not completely independent. 相似文献
13.
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
14.
Jean Bergeron Thierry Normand Adl Bharucha M. R. van Murtby Pierre Julien Claude Gagné Carole Dionne Marc de Braekeleer Daniel Brun Michael R. Hayden Paul J. Luplen 《Clinical genetics》1992,41(4):206-210
Familial lipoprotein lipase deficiency (FLD) is of particular interest to the French Canadian population of Québec since the largest concentration of homozygotes and carriers of this genetic disease in the world resides in this area. We have previously described a missense mutation (M-188) in the lipoprotein lipase (LPL) gene which was present in FLD patients belonging to different ancestries, including a number of French Canadians (Monsalve MV et al. J Clin Invest 1990: 86: 728-734). In the present report, we show that this mutation, although found in largest absolute numbers among French Canadians as compared to other groups in the world, accounts for only a small proportion (24%) of all the LPL mutant alleles in this population. The M-188 occurs either in the homozygote state or as a compound heterozygote with another LPL mutation. Analysis of geographic distribution indicates that the M-188 is more prevalent in western Québec, with the highest carrier rate in the Mauricie region. Genealogical reconstruction leads to the recognition of four founders for M-188, all emigrants from France to Québec in the 17th century. 相似文献
15.
Morning to evening changes in the electrical and mechanical properties of human soleus motor units activated by H reflex and M wave 总被引:2,自引:0,他引:2
The aim of the present study was to compare the relative contribution of the soleus motor units (MUs) activated by H and M
waves to the plantar-flexion torque in the morning and in the evening. Twelve healthy male subjects (physical education students)
took part in this investigation. The electromechanical properties of the plantar flexor muscles were recorded at two different
times of day: between 06:00 and 08:00 h and between 17:00 and 19:00 h. Plantar-flexion torque and concomitant electromyographic
activity of soleus muscle were assessed under voluntary and evoked conditions. The results indicated a significant decrease
in maximal voluntary muscle torque of triceps surae and associated soleus EMG in the evening as compared with the morning.
The mean values of MVC ranged from 131.6±9.6 N m in the morning to 125.1±9.0 N m in the evening. Peak-to-peak values of soleus
H
max and M
max potentials were comparable in the morning and in the evening (2.97 vs 3.18 mV and 7.95 vs 7.44 mV for H
max and M
max, respectively). The H
max/M
max ratio was not modified between the two experimental test sessions (34.8 vs 41.3%). The peak amplitude of the twitch produced
by the H
max wave
decreased significantly. When estimating the mechanical contribution to
of the slowest and fastest-twitch MUs reflexively and directly activated, we observed that the contribution of the slowest
MUs did not change while those of the fastest decreased significantly in the evening. To conclude, a weaker reflex twitch
torque caused by higher fatigue state of the MUs directly activated by the M wave which accompanied H
max in the evening may be regarded as a possible explanation of the weaker plantar-flexion torque production in the evening. 相似文献
16.
Doris Škorić‐Milosavljević Fleur V. Y. Tjong Julien Barc Ad P. C. M. Backx Sally‐Ann B. Clur Karin van Spaendonck‐Zwarts Roelof‐Jan Oostra Najim Lahrouchi Leander Beekman Regina Bökenkamp Daniela Q. C. M. Barge‐Schaapveld Barbara J. Mulder Elisabeth M. Lodder Connie R. Bezzina Alex V. Postma 《American journal of medical genetics. Part A》2019,179(9):1836-1845
The first human mutations in GATA6 were described in a cohort of patients with persistent truncus arteriosus, and the phenotypic spectrum has expanded since then. This study underscores the broad phenotypic spectrum by presenting two patients with de novo GATA6 mutations, both exhibiting complex cardiac defects, pancreatic, and other abnormalities. Furthermore, we provided a detailed overview of all published human genetic variation in/near GATA6 published to date and the associated phenotypes (n = 78). We conclude that the most common phenotypes associated with a mutation in GATA6 were structural cardiac and pancreatic abnormalities, with a penetrance of 87 and 60%, respectively. Other common malformations were gallbladder agenesis, congenital diaphragmatic hernia, and neurocognitive abnormalities, mostly developmental delay. Fifty‐eight percent of the mutations were de novo, and these patients more often had an anomaly of intracardiac connections, an anomaly of the great arteries, and hypothyroidism, compared with those with inherited mutations. Functional studies mostly support loss‐of‐function as the pathophysiological mechanism. In conclusion, GATA6 mutations give a wide range of phenotypic defects, most frequently malformations of the heart and pancreas. This highlights the importance of detailed clinical evaluation of identified carriers to evaluate their full phenotypic spectrum. 相似文献
17.
Daphné Lehalle Roberto Colombo Michael O'Grady Bénédicte Héron Nada Houcinat Paul Kuentz Sebastien Moutton Arthur Sorlin Julien Thevenon Julian Delanne Sebastien Gay Caroline Racine Aurore Garde Frédéric Tran Mau‐Them Christophe Philippe Antonio Vitobello Sophie Nambot Frédéric Huet Yannis Duffourd François Feillet Christel Thauvin‐Robinet Sandrine Marlin Laurence Faivre 《American journal of medical genetics. Part A》2019,179(9):1756-1763
Alpha‐mannosidosis (AM) is a very rare (prevalence: 1/500000 births) autosomal recessive lysosomal storage disorder. It is characterized by multi‐systemic involvement associated with progressive intellectual disability, hearing loss, skeletal anomalies, and coarse facial features. The spectrum is wide, from very severe and lethal to a milder phenotype that usually progresses slowly. AM is caused by a deficiency of lysosomal alpha‐mannosidase. A diagnosis can be established by measuring the activity of lysosomal alpha‐mannosidase in leucocytes and screening for abnormal urinary excretion of mannose‐rich oligosaccharides. Genetic confirmation is obtained with the identification of MAN2B1 mutations. Enzyme replacement therapy (LAMZEDER) was approved for use in Europe in August 2018. Here, we describe seven individuals from four families, diagnosed at 3–23 years of age, and who were referred to a clinical geneticist for etiologic exploration of syndromic hearing loss, associated with moderate learning disabilities. Exome sequencing had been used to establish the molecular diagnosis in five cases, including a two‐sibling pair. In the remaining two patients, the diagnosis was obtained with screening of urinary oligosaccharides excretion and the association of deafness and hypotonia. These observations emphasize that the clinical diagnosis of AM can be challenging, and that it is likely an underdiagnosed rare cause of syndromic hearing loss. Exome sequencing can contribute significantly to the early diagnosis of these nonspecific mild phenotypes, with advantages for treatment and management. 相似文献
18.
Brice Poreau Francis Ramond Radu Harbuz Véronique Satre Claire Barro Claire Vettier Véronique Adouard Julien Thevenon Pierre‐Simon Jouk Charles Coutton Klaus Dieterich 《American journal of medical genetics. Part A》2019,179(4):650-654
The AMME syndrome defined as the combination of Alport syndrome, intellectual disability, midface hypoplasia, and elliptocytosis (AMME) is known to be a contiguous gene syndrome associated with microdeletions in the region Xq22.3q23. Recently, using exome sequencing, missense pathogenic variants in AMMECR1 have been associated with intellectual disability, midface hypoplasia, and elliptocytosis. In these cases, AMMECR1 gene appears to be responsible for most of the clinical features of the AMME syndrome except for Alport syndrome. In this article, we present two unrelated male patients with short stature, mild intellectual disability or neurodevelopmental delay, sensorineural hearing loss, and elliptocytosis harboring small microdeletions identified by array‐CGH involving TMEM164 and AMMECR1 genes and SNORD96B small nucleolar RNA for one patient, inherited from their mothers. These original cases further confirm that most specific AMME features are ascribed to AMMECR1 haploinsufficiency. These cases reporting the smallest microdeletions encompassing AMMECR1 gene provide new evidence for involvement of AMMECR1 in the AMME phenotype and permit to discuss a phenotype related to AMMECR1 haploinsufficiency: developmental delay/intellectual deficiency, midface hypoplasia, midline defect, deafness, and short stature. 相似文献
19.
Igarashi S; Takiyama Y; Cancel G; Rogaeva EA; Sasaki H; Wakisaka A; Zhou YX; Takano H; Endo K; Sanpei K; Oyake M; Tanaka H; Stevanin G; Abbas N; Durr A; Rogaev EI; Sherrington R; Tsuda T; Ikeda M; Cassa E; Nishizawa M; Benomar A; Julien J; Weissenbach J; Tsuji S 《Human molecular genetics》1996,5(7):923-932
Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative
disorder caused by unstable expansion of a CAG repeat in the MJD1 gene at
14q32.1. To identify elements affecting the intergenerational instability
of the CAG repeat, we investigated whether the CGG/GGG polymorphism at the
3' end of the CAG repeat affects intergenerational instability of the CAG
repeat. The [expanded (CAG)n-CGG]/[normal (CAG)n- GGG] haplotypes were
found to result in significantly greater instability of the CAG repeat
compared to the [expanded (CAG)n- CGG]/[normal (CAG)n-CGG] or [expanded
(CAG)nGGG]/[normal (CAG)n-GGG] haplotypes. Multiple stepwise logistic
regression analysis revealed that the relative risk for a large
intergenerational change in the number of CAG repeat units (< -2 or >
2) is 7.7-fold (95% CI: 2.5-23.9) higher in the case of paternal
transmission than in that of maternal transmission and 7.4-fold (95% CI:
2.4-23.3) higher in the case of transmission from a parent with the
[expanded (CAG)n-CGG]/[normal (CAG)n-GGG] haplotypes than in that of
transmission from a parent with the [expanded (CAG)n-CGG]/[normal
(CAG)n-CGG] or [expanded (CAG)n- GGG]/[normal (CAG)n-GGG] haplotypes. The
combination of paternal transmission and the [expanded (CAG)n-CGG]/[normal
(CAG)n-GGG] haplotypes resulted in a 75.2-fold (95% CI: 9.0-625.0) increase
in the relative risk compared with that of maternal transmission and the
[expanded (CAG)n-CGG]/[normal (CAG)n-CGG] or [expanded (CAG)n- GGG]/[normal
(CAG)n-GGG] haplotypes. The results suggest that an inter- allelic
interaction is involved in the intergenerational instability of the
expanded CAG repeat.
相似文献
20.
Loubinoux J Rio B Mihaila L Foïs E Le Fleche A Grimont PA Marie JP Bouvet A 《Journal of clinical microbiology》2005,43(7):3564-3566
A yellow-pigmented rod- to coccoid-shaped coryneform microorganism was isolated from the blood of a patient with acute myeloid leukemia. It was identified by 16S rRNA gene sequencing as a previously undescribed species of Janibacter. The isolate was susceptible to penicillins, aminoglycosides, fluoroquinolones, and glycopeptides. 相似文献