全文获取类型
收费全文 | 542篇 |
免费 | 34篇 |
国内免费 | 8篇 |
专业分类
耳鼻咽喉 | 3篇 |
儿科学 | 7篇 |
妇产科学 | 8篇 |
基础医学 | 87篇 |
口腔科学 | 7篇 |
临床医学 | 36篇 |
内科学 | 129篇 |
皮肤病学 | 8篇 |
神经病学 | 102篇 |
特种医学 | 5篇 |
外科学 | 33篇 |
综合类 | 36篇 |
预防医学 | 37篇 |
眼科学 | 2篇 |
药学 | 58篇 |
中国医学 | 14篇 |
肿瘤学 | 12篇 |
出版年
2023年 | 2篇 |
2022年 | 5篇 |
2021年 | 10篇 |
2020年 | 13篇 |
2019年 | 26篇 |
2018年 | 27篇 |
2017年 | 18篇 |
2016年 | 13篇 |
2015年 | 14篇 |
2014年 | 29篇 |
2013年 | 38篇 |
2012年 | 30篇 |
2011年 | 36篇 |
2010年 | 39篇 |
2009年 | 26篇 |
2008年 | 29篇 |
2007年 | 40篇 |
2006年 | 24篇 |
2005年 | 14篇 |
2004年 | 19篇 |
2003年 | 24篇 |
2002年 | 15篇 |
2001年 | 10篇 |
2000年 | 6篇 |
1999年 | 7篇 |
1998年 | 4篇 |
1997年 | 2篇 |
1996年 | 4篇 |
1995年 | 1篇 |
1993年 | 1篇 |
1992年 | 1篇 |
1990年 | 1篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1986年 | 3篇 |
1985年 | 12篇 |
1984年 | 7篇 |
1983年 | 3篇 |
1982年 | 10篇 |
1981年 | 3篇 |
1980年 | 2篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1977年 | 2篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1973年 | 1篇 |
排序方式: 共有584条查询结果,搜索用时 15 毫秒
111.
Nucleosides are neuromodulators that participate in various neuronal functions in the brain. In previous studies, we described regional differences in the concentrations of nucleosides and their derivatives in the human brain. To better understand the functions of nucleosides in the central nervous system, we investigated gender- and age-dependent changes in the levels of nucleosides and their metabolites. The concentrations of uridine, inosine, guanosine and adenosine as well as uracil, hypoxanthine and xanthine were measured in the frontal cortex and white matter of post-mortem brain tissue samples of middle-aged and old men as well as women. The average in vivo concentrations calculated from the 40 samples investigated (regardless of anatomical locations, gender or age; mean ± S.E.M.) were as follows (pmol/mg wet tissue weight): 9.7 ± 0.8 adenosine, 85.8 ± 3.9 inosine, 14.3 ± 0.9 guanosine, 37.3 ± 1.8 uridine, 8.9 ± 0.6 uracil, 63.3 ± 2.1 hypoxanthine and 38.7 ± 1.5 xanthine. We conclude that concentration differences between uridine, inosine, guanosine and adenosine in the frontal cortex and cerebral white matter suggest that nucleoside metabolism is altered with aging and regulated differently between men and women. 相似文献
112.
Caroline Dubertret Claire Bardel Nicolas Ramoz Pierre-Marie Martin Jean-Charles Deybach Jean Adès Philip Gorwood Laurent Gouya 《Progress in neuro-psychopharmacology & biological psychiatry》2010
Background
The gene coding for the D2 dopamine receptor (DRD2) is considered to be one of the most pertinent candidate genes in schizophrenia. However, genetic studies have yielded conflicting results whereas the promising TaqIA variant/rs1800497 has been mapped in a novel gene, ANKK1.Methods
We investigated eleven single nucleotide polymorphisms (SNPs) spanning the DRD2 and ANKK1 genes, using both a case–control association study comparing 144 independent patients to 142 matched healthy subjects, and a transmission disequilibrium test in 108 trios. This classical genetic study was coupled with a cladistic phylogeny-based association test of human variants, and with an interspecies evolution study of ANKK1.Results
Case–control study, followed by a 108 trios family-based association analysis for replication, revealed an association between schizophrenia and the ANKK1 rs1800497 (p = 0.01, Odds Ratio = 1.5, 95% Confidence Interval = 1.1–2.2), and the intergenic rs2242592 (p = 2 · 10− 4, OR = 1.8, 95%CI = 1.3–2.5). A significant SNP–SNP interaction was also found (p < 10− 5, OR = 2.0, 95%CI = 1.6–2.5). The phylogeny-based association test also identified an association between both these polymorphisms and schizophrenia. Finally, interspecies comparison of the sequences from chimpanzee, orangutan, rhesus macaque and human species suggested specific involvement of ANKK1 in the human lineage.Conclusions
Intergenic rs2242592 appears to be involved in the genetic vulnerability to schizophrenia, whereas the ANKK1 rs1800497 appears to have a modifying rather than causative effect. Finally, ANKK1 may be a specific human lineage-trait involved in a specific human disease, schizophrenia. 相似文献113.
114.
K. Natalie Randles Le Thanh Lam Caroline A. Sewry Megan Puckelwartz Denis Furling Manfred Wehnert Elizabeth M. McNally Glenn E. Morris 《Developmental dynamics》2010,239(3):998-1009
Nesprins are a family of nuclear transmembrane proteins anchored via Sun proteins to the nuclear membrane. Analysis of nesprins during human muscle development revealed an increase in nesprin‐1‐giant during early myogenesis in vitro. During the transition from immature to mature muscle fibres in vivo, nesprin‐2 partly replaced nesprin‐1 at the nuclear envelope and short nesprin isoforms became dominant. Sun1 and Sun2 proteins remained unchanged during this fibre maturation. In emerin‐negative skin fibroblasts, nesprin‐2‐giant was relocated from the nuclear envelope to the cytoplasm, not to the endoplasmic reticulum, while nesprin‐1 remained at the nuclear envelope. In emerin‐negative keratinocytes lacking nesprin‐1, nesprin‐2 remained at the nuclear envelope. HeLa cell nuclear envelopes lacked nesprin‐1, which was the dominant form in myoblasts, while a novel 130‐kD nesprin‐2 isoform dominated Ntera‐2 cells. The results suggest the possibility of isoform‐specific and tissue‐specific roles for nesprins in nuclear positioning. Developmental Dynamics 239:998–1009, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
115.
Sita Javeri Michael Rodi Magdalena Tary-Lehmann Paul V. Lehmann Klaus Addicks Stefanie Kuerten 《Clinical immunology (Orlando, Fla.)》2010,137(2):181-189
The role of brain-derived neurotrophic factor (BDNF) in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE) is still unclear. Here we investigate the clinical course, CNS histopathology and peripheral antigen-specific immunity in MP4-induced EAE of BDNF (−/+) mice. We demonstrate that these mice displayed less severe disease compared to BDNF (+/+) mice, reflected by decreased inflammation and demyelination. In correspondence to diminished frequencies of T and B cells in CNS infiltrates, the peripheral MP4-specific TH1/TH17 response was attenuated in BDNF (−/+), but not in wild-type animals. In contrast, immunization with ovalbumin triggered similar frequencies of IFN-γ- and IL-17-secreting T cells in both groups. The cytokine secretion and proliferative activity upon mitogen stimulation did not reveal any global defect of T cell function in BDNF (−/+) mice. By influencing the antigen-specific immune response in autoimmune encephalomyelitis, BDNF may support and maintain the disease in ways that go beyond its alleged neuroprotective role. 相似文献
116.
目的将含有目的基因NT3的重组腺病毒Ad-DsRed2-NT3转染新生小鼠的离体耳蜗基底膜培养组织,观察其在预防庆大霉素的耳毒性中的作用。方法取新生小鼠的耳蜗基底膜离体培养1d后,用含有目的基因NT3的重组腺病毒Ad-DsRed2-NT3转染新生小鼠的离体耳蜗基底膜培养组织,转染成功1d后用终浓度为3mM的庆大霉素对离体耳蜗基底膜造模,造模3d后,行离体耳蜗基底膜的神经微丝免疫荧光染色,观察各组耳蜗基底膜神经微丝的密度,以观测NT3对离体耳蜗基底膜上的螺旋神经的保护作用。结果新生小鼠的离体耳蜗基底膜生长良好,重组腺病毒Ad-DsRed2-NT3能对其有效转染,庆大霉素造模后3d各组耳蜗基底膜神经微丝的密度(每100μm距离内的螺旋神经微丝数)分别为(±s):造模组16.67±1.63、Ad-DsRed2组16.17±2.31、Ad-DsRed2-NT3组40.33±1.63、空白组为43.17±0.75,其中,造模组与空白组、Ad-DsRed2-NT3组与造模组、Ad-DsRed2-NT3组与Ad-DsRed2组之间具有显著性统计学差异(P<0.05)。结论终浓度为3mM的庆大霉素对小鼠离体耳蜗基底膜上的螺旋神经有明显的损害作用,而NT3基因的过表达对这种损害具有保护作用。 相似文献
117.
Thomas Rossor Ming Lim Kirandeep VanDenEshof Paul Gringras 《European journal of paediatric neurology》2018,22(1):194-198
Type 1 narcolepsy (NT1) is a chronic primary disorder of hypersomnolence characterized by excessive daytime sleepiness, cataplexy, sleep paralysis, hypnagogic hallucinations and disrupted nocturnal sleep.NT1 is linked to hypothalamic hypocretin deficiency, strongly associated with Human Leukocyte Antigen (HLA) marker DQB1*06:02 and of probable autoimmune origin. NT1 is usually associated with increased rates of overweight and obesity, and sometimes with increases in overnight blood pressure and increased rates of hypoventilation with raised CO2 levels overnight. Many of these are predisposing factors for pseudotumor cerebri syndrome (PTCS).We present a case of a young girl with both NT1 and PTCS that responded well to treatment with acetazolamide after early identification, with improvement of headache and resolution of hypoventilation. 相似文献
118.
The primate amygdala is composed of multiple subnuclei that play distinct roles in amygdala function. While some nuclei have been areas of focused investigation, others remain virtually unknown. One of the more obscure regions of the amygdala is the paralaminar nucleus (PL). The PL in humans and non-human primates is relatively expanded compared to lower species. Long considered to be part of the basal nucleus, the PL has several interesting features that make it unique. These features include a dense concentration of small cells, high concentrations of receptors for corticotropin releasing hormone and benzodiazepines, and dense innervation of serotonergic fibers. More recently, high concentrations of immature-appearing cells have been noted in the primate PL, suggesting special mechanisms of neural plasticity. Following a brief overview of amygdala structure and function, this review will provide an introduction to the history, embryology, anatomical connectivity, immunohistochemical and cytoarchitectural properties of the PL. Our conclusion is that the PL is a unique subregion of the amygdala that may yield important clues about the normal growth and function of the amygdala, particularly in higher species. 相似文献
119.
LW Law TK Lau TY Fung TY Leung CC Wang KW Choy 《BJOG : an international journal of obstetrics and gynaecology》2009,116(2):339-343
Objective We investigated the application of high-resolution microarray-based comparative genomic hybridisation (array CGH) on a fetus showing increased nuchal translucency (NT).
Design Case study.
Setting Tertiary referral obstetrics unit.
Sample Pregnant woman attended the antenatal clinic.
Methods Conventional karyotyping and genetic test was carried out for the alpha-globin gene. High-resolution array CGH using the high-density 244K Agilent microarray was performed on fetal blood sample by cordocentesis to investigate the possibility of any genomic imbalance.
Main outcome measures Detection of chromosomal abnormality.
Results Karyotyping analysis showed 46,XY. Molecular genetic diagnosis confirms the fetus has Hb-H constant spring disease but cannot explain the increased NT to 3.2 mm. Array CGH analysis discovered a 1.32-Mb microdeletion on chromosome 16p13.11. Deletion at 16p13.11 has been implicated to predispose to autism and/or mental retardation. Baby was delivered at 40 weeks of gestation, and follow up was carried out at 3 months of age without sign of mental retardation/developmental delay.
Conclusions This case study demonstrated that array CGH can accurately calibrate the size and identify de novo interstitial chromosome imbalances. However, the presence of chromosome copy variants with unknown clinical significance currently limits its wider scale application in prenatal diagnosis and needs further investigations. 相似文献
Design Case study.
Setting Tertiary referral obstetrics unit.
Sample Pregnant woman attended the antenatal clinic.
Methods Conventional karyotyping and genetic test was carried out for the alpha-globin gene. High-resolution array CGH using the high-density 244K Agilent microarray was performed on fetal blood sample by cordocentesis to investigate the possibility of any genomic imbalance.
Main outcome measures Detection of chromosomal abnormality.
Results Karyotyping analysis showed 46,XY. Molecular genetic diagnosis confirms the fetus has Hb-H constant spring disease but cannot explain the increased NT to 3.2 mm. Array CGH analysis discovered a 1.32-Mb microdeletion on chromosome 16p13.11. Deletion at 16p13.11 has been implicated to predispose to autism and/or mental retardation. Baby was delivered at 40 weeks of gestation, and follow up was carried out at 3 months of age without sign of mental retardation/developmental delay.
Conclusions This case study demonstrated that array CGH can accurately calibrate the size and identify de novo interstitial chromosome imbalances. However, the presence of chromosome copy variants with unknown clinical significance currently limits its wider scale application in prenatal diagnosis and needs further investigations. 相似文献
120.
目的探讨血清α-L-岩藻糖苷酶(AFU)、5′-核苷酸酶(5′NT)和γ-谷氨酰转肽酶(γ-GGT)在原发性肝癌检测中的意义。方法设定原发性肝癌组52例,肝硬化组36例,健康对照组103例,测定各组的AFU、5′NT和γ-GGT水平,单独测定甲胎蛋白(AFP)在原发性肝癌组的水平。结果 52例原发性肝癌患者中,AFP6.7 U/mL阳性者为37例,检出率为71.15%,而AFU、5′NT和γ-GGT联合检出阳性者为43例,阳性率为82.69%。原发性肝癌组的AFU、5′NT和γ-GGT水平比单检AFP水平敏感性高。结论 AFU、5′NT和γ-GGT联合检测可弥补AFP低水平的不足,是一个诊断原发性肝癌的有效血清酶学指标。AFU、5′NT和γ-GGT对原发性肝癌的诊断敏感性、特异性各有所长,联合应用可优势互补,阳性率可显著提高,对临床诊断及判断病情,疾病的转归有重要意义。 相似文献