全文获取类型
收费全文 | 4145篇 |
免费 | 95篇 |
国内免费 | 92篇 |
专业分类
耳鼻咽喉 | 40篇 |
儿科学 | 226篇 |
妇产科学 | 81篇 |
基础医学 | 954篇 |
口腔科学 | 32篇 |
临床医学 | 247篇 |
内科学 | 1050篇 |
皮肤病学 | 48篇 |
神经病学 | 740篇 |
特种医学 | 44篇 |
外科学 | 206篇 |
综合类 | 178篇 |
预防医学 | 171篇 |
眼科学 | 70篇 |
药学 | 129篇 |
1篇 | |
中国医学 | 3篇 |
肿瘤学 | 112篇 |
出版年
2023年 | 46篇 |
2022年 | 112篇 |
2021年 | 144篇 |
2020年 | 121篇 |
2019年 | 162篇 |
2018年 | 153篇 |
2017年 | 116篇 |
2016年 | 110篇 |
2015年 | 131篇 |
2014年 | 221篇 |
2013年 | 237篇 |
2012年 | 164篇 |
2011年 | 210篇 |
2010年 | 146篇 |
2009年 | 192篇 |
2008年 | 248篇 |
2007年 | 163篇 |
2006年 | 179篇 |
2005年 | 146篇 |
2004年 | 119篇 |
2003年 | 117篇 |
2002年 | 87篇 |
2001年 | 82篇 |
2000年 | 65篇 |
1999年 | 68篇 |
1998年 | 55篇 |
1997年 | 46篇 |
1996年 | 38篇 |
1995年 | 46篇 |
1994年 | 38篇 |
1993年 | 37篇 |
1992年 | 27篇 |
1991年 | 23篇 |
1990年 | 20篇 |
1989年 | 19篇 |
1988年 | 23篇 |
1987年 | 11篇 |
1986年 | 10篇 |
1985年 | 60篇 |
1984年 | 53篇 |
1983年 | 38篇 |
1982年 | 46篇 |
1981年 | 48篇 |
1980年 | 36篇 |
1979年 | 29篇 |
1978年 | 19篇 |
1977年 | 15篇 |
1976年 | 12篇 |
1975年 | 11篇 |
1974年 | 14篇 |
排序方式: 共有4332条查询结果,搜索用时 265 毫秒
21.
Jennifer A. Ruskey Lior Greenbaum Léanne Roncière Armaghan Alam Dan Spiegelman Christopher Liong Oren A. Levy Cheryl Waters Stanley Fahn Karen S. Marder Wendy Chung Gilad Yahalom Simon Israeli-Korn Vered Livneh Tsvia Fay-Karmon Roy N. Alcalay Sharon Hassin-Baer Ziv Gan-Or 《European journal of medical genetics》2019,62(1):65-69
Background
Variants in GBA are the most common genetic risk factor for Parkinson's disease (PD), and are especially prevalent in the Ashkenazi Jewish (AJ) population. However, most studies on GBA in AJ genotype only seven selected Gaucher-associated pathogenic variants rather than sequencing the whole gene, which may leave carriers of PD-associated GBA variants undiscovered.Methods
GBA was fully sequenced using molecular inversion probes (MIPs) and Sanger sequencing in 735 AJ PD patients and 662 AJ controls, from Israel and New York. Additional AJ control data (n?=?3044) from the Inflammatory Bowel Disease Exome Portal was used.Results
Full GBA sequencing increased the number of variants discovered by 17.4%, compared to targeted genotyping. An additional 17 PD patients were identified with GBA-associated PD. The p.E326K variant was found in 1.6% of AJ PD patients, making it the second most common PD-associated GBA variant in AJ. GBA variants were found in 18% of PD patients and 7.5% of controls (OR?=?2.7, 95%CI?=?1.9–3.8, p?<?0.0001).Conclusion
Without full sequencing of GBA, or at minimum including p.E326K in the genotyping panel, a significant proportion of variant carriers go undiscovered and may be incorrectly assigned as non-carriers in studies or clinical trials. 相似文献22.
R.S.K. Chaganti Roller B. Bailey Suresh C. Jhanwar Zalmen A. Arlin Bayard D. Clarkson 《Cancer Genetics and Cytogenetics》1982,5(3):215-221
Malignancy in patients with constitutional chromosome abnormality is of interest not only because it permits insights into the relationship between chromosome abnormality and cancer, but also because it provides opportunities to address such questions as the clonality and evolution of tumors. We report Ph1-positive chronic myelogenous leukemia (CML) in a 50-year-old mosaic (45,X/46,XX) Turner syndrome patient whose leukemia was restricted to the monosomic cell line. Our extensive cytogenetic studies of this patient demonstrated that non-leukemic normal cells persisted in the marrow and were able to proliferate during a period of temporary suppression of the leukemic clone following aggressive treatment. 相似文献
23.
A monoclonal antibody specific for human alpha-fetoprotein (HAFP) was derived by the hybridoma technique. Spleen cells from mice immunized with pure HAFP were fused with a mouse myeloma cell line (P3×63-Ag-8) and an anti-HAFP secreting hybridoma cell line was cloned in soft agarose. The HAFP specific antibody was shown to be a monoclonal IgG1 subclass with extremely high avidity for HAFP. 相似文献
24.
Younyoung Kim Jin-Hyuck Kim Yu Jin Nam Minyoung Kong Yun Joong Kim Kyung-Ho Yu Byung-Chul Lee Chaeyoung Lee 《Neuroscience letters》2006
An aging-suppressor gene, klotho, is a candidate factor for vascular disease because its deficiency leads to impaired endothelium-dependent vasodilation and impaired angiogenesis. We investigated the association of polymorphisms in klotho with ischemic stroke. We searched for sequence variants in promoter and exons of klotho gene. For the association study, selected variants were genotyped in control subjects and in patients with ischemic stroke and vascular dementia. The association with ischemic stroke was further investigated with its subtypes classified based on Trial of Org 10172 in Acute Stroke Treatment (TOAST). No significant association was observed for both G-395A and C1818T with ischemic stroke and vascular dementia (P > 0.05). The analysis with subtypes of ischemic stroke revealed the associations that the A allele of G-395A increased the risk of cardioembolic stroke (CE, OR = 2.60; P = 0.006), and subjects carrying the A allele were susceptible to CE in both of dominant (AA + GA versus GG; OR = 2.50; P = 0.046) and recessive (AA versus GA + GG; OR = 6.52; P = 0.007) models. Further analysis of data partitioned by gender showed that the associations of G-395A with CE only existed in women (A versus G; OR = 4.33; P = 0.002), AA + GA versus GG; OR = 5.68; P = 0.014, and AA versus GA + GG; OR = 9.07; P = 0.012), but the significance disappeared in men (P > 0.05). The sequence variant of G-395A in klotho might be a genetic risk factor for CE in females. 相似文献
25.
ACE Genotype May Have an Effect on Single versus Multiple Set Preferences in Strength Training 总被引:1,自引:0,他引:1
Colakoglu M Cam FS Kayitken B Cetinoz F Colakoglu S Turkmen M Sayin M 《European journal of applied physiology》2005,95(1):20-26
A polymorphic variant of the human angiotensin converting enzyme (ACE) gene was identified. The 'D' (rather than 'I') variant was associated with improvements in strength related to physical training. We set out to determine whether the response to different patterns of strength training might also differ. Ninty-nine Caucasian male non-elite athletes were randomly allocated into one of three groups: 31 non-training/control (CG: 31), single-set (SSG: 35) and multiple-set (MSG: 33). SSG and MSG trained three times a week for 6 weeks. Both training groups were underwent a strength-training program with two mesocycles (12-15 repetition maximum (RM) and 8-12 RM mesocycles). One RM loads in half squat and bench press were assessed before training and after the first and second mesocycles. ACE polymorphisms analysed by polymerase chain reaction (PCR) methods. Subjects with ACE II genotype in the MST group had improved strength development in 12-15 RM, while SST and MST groups had similar gains in 8-12 RM. Subjects with ACE DD genotype in both the SSG and the MSG had similar benefits from both 12-15 RM and 8-12 RM. Strength gains for subjects with ACE ID genotype in the SSG were similar to MSG gains in response to 8-12 RM loads but not with 12-15 RM loads. Additionally, subjects with DD genotype had superior strength gains in both strength training groups. Tailoring strength training programmes (single-set vs. multiple set) according to the athlete's ACE genotype may be advantageous. 相似文献
26.
The familial prevalence in second-degree relatives of patients with anxiety neurosis (panic disorder) 总被引:1,自引:0,他引:1
A family history study of second-degree relatives of 19 patients with anxiety neurosis (panic disorder) and 19 controls showed a morbidity risk of 9.5% among the former compared with 1.4% among the latter. These risks were approximately half those found among first-degree relatives. Female relatives were at higher risk for anxiety neurosis. The risk for other psychiatric illnesses did not differ between the relatives of anxiety neurosis and controls. 相似文献
27.
Temperature-sensitive mutants of reovirus type 3 are capable of interfering with the replication of wild-type reovirus type 3. The interfering activity correlated with the ability of pairs of mutants to complement at 39°: Pairs of noninterfering mutants (tsD × tsE) yielded efficient complementation (indexes of 10–50); pairs of interfering mutants (including members of groups ts A, B, G) did not produce significant complementation (indexes ~ 1). The ability of pairs of mutants to reassort at 39° generally followed a similar pattern. Thus interference is an important property of ts mutants of reovirus and needs to be considered when genetic interactions are being studied at 39°. 相似文献
28.
Price TS Simonoff E Asherson P Curran S Kuntsi J Waldman I Plomin R 《Behavior genetics》2005,35(2):121-132
The genetic and environmental mediation of continuity and change in parent-reported ADHD symptoms were investigated in a cohort of over 6000 twin pairs at 2, 3 and 4 years of age. Genetic analyses of the cross-sectional data yielded heritability estimates of 0.78–0.81 at each age, with contrast effects. A common pathway model provided the best fit to the longitudinal data, indicating that genetic influences underlie 91% of the stable variance in ADHD symptomatology. In other words, what is stable for ADHD symptoms is largely genetic. Contrast effects acting in the same direction at different ages contributed to the observed continuity:longitudinal correlations were greater for dizygotic than monozygotic twins.The Twins Early Development Study is funded by the Medical Research Council. 相似文献
29.
In this review, we have summarized our work using combined complex statistical genetics, bioinformatics, and functional genomics to determine the genetic basis of the age-related thymic involution in C57BL/6J X DBA/2J recombinant inbred mice and the parental B6 and D2 mice. We have shown that these mice provided a valuable genetic model that can permit resampling of thymuses from different aged but genetically identical animals and determination of the relative significance of age-associated changes in the thymus. Our results suggest that the quantitative trait loci (QTL) regulating the Con A-induced thymocyte proliferative response were mapped to mouse chromosome Chr 11 (D11Mit51 at 18 cM), a region that harbors the IL-12b gene. The importance of IL-12b in maintaining thymic integrity and function during the aging process was confirmed by a more rapid involution of the thymus in IL-12b knockout (IL-12b-/-) mice compared to wild-type (WT) mice. Functionally, IL-12 provided a strong synergistic effect to augment the IL-7 or IL-2 induced thymocyte proliferative response, especially in both aged WT and IL-12b-/- mice, but not in normal young mice. In contract to the proliferative response, the age-related decline in the total number of thymocytes was determined at different age, and mapped to loci on Chr 9, 62 cM and Chr 10, 32 cM. Using matrix-assisted laser desorption/ionisation-time of flight-mass spectrometry (MALDI-TOF-MS), increased expression of peroxiredoxin was found to be correlated with thymic involution. Our results suggest the possibility to identify the complex molecular network that can be associated with the regulation of thymic involution in aged mice using a high-dimensional functional genomics approach. 相似文献
30.
The methionine allele of the COMT polymorphism impairs prefrontal cognition in children and adolescents with ADHD 总被引:9,自引:0,他引:9
Bellgrove MA Domschke K Hawi Z Kirley A Mullins C Robertson IH Gill M 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2005,163(3):352-360
ADHD is a highly heritable psychiatric disorder of childhood. A functional polymorphism (Val158Met) of the catechol-O-methyltransferase (COMT) gene has attracted interest as a candidate gene for ADHD. The high-activity valine variant of this polymorphism degrades prefrontal dopamine three to four times more quickly than the low-activity methionine variant and could therefore contribute to the proposed hypodopaminergic state in ADHD. Here we tested for association of this polymorphism with ADHD and examined its influence on prefrontal cognition in ADHD. We have previously reported no association of the Val158Met COMT gene polymorphism in 94 Irish ADHD families (Hawi et al. (2000) Am J Med Genet 96:282–284). Here we re-examined this finding with an extended sample of 179 ADHD cases using a family control design. We also examined the performance of children and adolescents with ADHD (n=61) on a standardised test of sustained attention. Analysis confirmed the absence of an association between the Val158Met COMT gene polymorphism and the clinical phenotype of ADHD. COMT genotype, however, affected prefrontal cognition in ADHD: ADHD children who were homozygous for the valine variant had significantly better sustained attention than those ADHD children possessing at least one copy of the methionine variant. Children possessing the methionine variant performed significantly below age-related norms on tests of sustained attention. Contrary to expectations, the methionine variant of the Val158Met COMT gene polymorphism impaired prefrontally-mediated cognition in ADHD. This effect may be understood by positing a hyper-functioning of prefrontal dopaminergic systems. Against this background, the slower clearance of dopamine associated with the methionine variant of the COMT gene polymorphism may be disadvantageous to cognition in ADHD.Mark Bellgrove and Katharina Domschke contributed equally to this work and should therefore both be considered first authors. The work reported herein was supported by a grant from the Irish Health Research Board. 相似文献