全文获取类型
收费全文 | 129篇 |
免费 | 14篇 |
国内免费 | 2篇 |
专业分类
儿科学 | 7篇 |
基础医学 | 22篇 |
口腔科学 | 6篇 |
临床医学 | 8篇 |
内科学 | 18篇 |
皮肤病学 | 2篇 |
神经病学 | 3篇 |
特种医学 | 29篇 |
外科学 | 12篇 |
综合类 | 3篇 |
预防医学 | 3篇 |
眼科学 | 4篇 |
药学 | 17篇 |
肿瘤学 | 11篇 |
出版年
2022年 | 1篇 |
2021年 | 4篇 |
2020年 | 1篇 |
2018年 | 3篇 |
2017年 | 4篇 |
2016年 | 2篇 |
2015年 | 5篇 |
2014年 | 1篇 |
2013年 | 1篇 |
2012年 | 5篇 |
2011年 | 2篇 |
2010年 | 5篇 |
2009年 | 5篇 |
2008年 | 3篇 |
2007年 | 4篇 |
2006年 | 2篇 |
2005年 | 1篇 |
2004年 | 1篇 |
2003年 | 1篇 |
2002年 | 3篇 |
1999年 | 2篇 |
1998年 | 11篇 |
1997年 | 14篇 |
1996年 | 9篇 |
1995年 | 4篇 |
1994年 | 1篇 |
1993年 | 1篇 |
1992年 | 5篇 |
1991年 | 3篇 |
1989年 | 2篇 |
1988年 | 4篇 |
1987年 | 5篇 |
1986年 | 3篇 |
1985年 | 8篇 |
1984年 | 2篇 |
1983年 | 4篇 |
1981年 | 3篇 |
1980年 | 2篇 |
1977年 | 1篇 |
1976年 | 3篇 |
1975年 | 1篇 |
1970年 | 1篇 |
1967年 | 1篇 |
1966年 | 1篇 |
排序方式: 共有145条查询结果,搜索用时 11 毫秒
1.
2.
Identification of a gene disrupted by a microdeletion in a patient with X-linked retinitis pigmentosa (XLRP) 总被引:2,自引:2,他引:2
Roepman R; Bauer D; Rosenberg T; van Duijnhoven G; van de Vosse E; Platzer M; Rosenthal A; Ropers HH; Cremers FP; Berger W 《Human molecular genetics》1996,5(6):827-833
The gene for the most frequent from of X-linked retinitis pigmentosa
(XLRP), RP3, has been assigned by genetic and physical mapping to a segment
of less than 1000 kbp, which is flanked by the marker DXS1110 and the
ornithine transcarbamylase (OTC) gene. In search of microdeletions, we have
screened the DNA of 30 unrelated patients with XLRP by employing a
representative set of YAC-derived DNA fragments that were generated by
restriction enzyme digestion and PCR amplification. In one of these
patients, a 6.4 kbp microdeletion was detected which was not present in the
DNA of 444 male controls. A cosmid contig spanning the deletion was
constructed and used to isolate cDNAs from retina-specific libraries. Exons
corresponding to these expressed sequences as well as other putative exons
were identified by sequencing more than 30 kbp of the critical region. So
far, no point mutations in these putative exon sequences have been
identified.
相似文献
3.
Positional cloning of the gene for X-linked retinitis pigmentosa 3: homology with the guanine-nucleotide-exchange factor RCC1 总被引:6,自引:7,他引:6
Roepman R; van Duijnhoven G; Rosenberg T; Pinckers AJ; Bleeker-Wagemakers LM; Bergen AA; Post J; Beck A; Reinhardt R; Ropers HH; Cremers FP; Berger W 《Human molecular genetics》1996,5(7):1035-1041
The gene for retinitis pigmentosa 3 (RP3), the most frequent form of X-
linked RP (XLRP), has been mapped previously to a chromosome interval of
less than 1000 kbp between the DXS1110 marker and the OTC locus at
Xp21.1-p11.4. Employing a novel technique, YAC Representation Hybridization
(YRH)', we have recently identified a small XLRP associated microdeletion
in this interval, as well as several putative exons including the 3' end of
a gene that was truncated by the deletion. cDNA library screening and
sequencing of a cosmid centromeric to the deletion has now enabled us to
identify numerous additional exons and to detect several point mutations in
patients with XLRP. The predicted gene product shows homology to RCC1, the
guanine-nucleotide- exchange factor (GEF) of the Ras-like GTPase Ran. Our
findings suggest that we have cloned the long-sought RP3 gene, and that it
may encode the GEF of a retina-specific GTP-binding protein.
相似文献
4.
Comprehensive mutational scanning of the p53 coding region by two- dimensional gene scanning 总被引:2,自引:0,他引:2
A comprehensive mutational scanning test for the p53 coding region based on
multiplex PCR and two-dimensional DNA electrophoresis was designed and
evaluated. In a 2-step multiplex PCR, the p53 coding region (exons 2-11)
was amplified as a single 8646-bp fragment by long- distance PCR in step
one. This fragment served as a template for the subsequent co-amplification
of the individual exons in two multiplex groups in step two. The multiplex
products were then separated, first on the basis of size in non-denaturant
polyacrylamide gels and then on the basis of sequence by denaturing
gradient gel electrophoresis (DGGE). Primers for optimal PCR, melting
behavior and 2-D gel distribution were designed using a recently developed
computer program. The resulting two-dimensional gene scanning (TDGS) test
was evaluated by screening, in a blinded fashion, 29 coded DNA samples from
Li- Fraumeni syndrome patients with previously identified germline
mutations. All mutations were correctly detected. This assay provides an
accurate, cost-effective and non-radioactive method for simultaneous
mutational scanning of all p53 coding exons.
相似文献
5.
FP Robertson D Tsironis BR Davidson 《Annals of the Royal College of Surgeons of England》2015,97(5):e77-e78
Diaphragmatic lesions are usually congenital bronchogenic cysts. A patient with a known diaphragmatic cyst presented with new onset right upper quadrant pain. Repeat imaging showed enlargement of the cyst, the CA19–9 cancer marker was raised at 312iu/ml (normal: <27iu/ml) and positron emission tomography combined with computed tomography showed focally increased uptake in the cystic wall. In view of symptoms and risk of neoplasia, the lesion was excised. Histology showed a benign epidermoid cyst. Features falsely suggesting neoplasia have been reported previously with benign splenic cysts but not with a benign diaphragmatic epidermoid cyst. 相似文献
6.
Gallo A Cuozzo C Esposito I Maggiolini M Bonofiglio D Vivacqua A Garramone M Weiss C Bohmann D Musti AM 《Oncogene》2002,21(42):6434-6445
7.
Philip J Warelow B Nurs M Nurs S RPN RCN FP Cert AFP Cert 《Journal of advanced nursing》1996,24(4):655-661
This paper will examine the claim that caring is an appropriate ethical ideal for nursing. Initially it will examine nursing's philosophy of care and caring, highlighting some areas of difficulty and dissatisfaction articulated by many of its contemporary theorists Evaluation of the notion of caring as an appropriate ethical ideal for nursing will be balanced against those in opposition, and in this process their critique will be discussed This discussion will focus on areas such as virtue, virtue ethics, moral responsibility, feminine values, mothering and the debate between male and female caring Different forms of caring will be evaluated and balanced against different forms of nursing The paper will then suggest that current views which hold aloft nursing as a bedmate of caring may be detrimental to both the cared-for and the carer, advocating in the process a move toward change 相似文献
8.
Bianca A. Silva Camilla Mattucci Piotr Krzywkowski Rachel Cuozzo Laura Carbonari Cornelius T. Gross 《The European journal of neuroscience》2016,43(11):1431-1439
The amygdala has been shown to be essential for the processing of acute and learned fear across animal species. However, the downstream neural circuits that mediate these fear responses differ according to the nature of the threat, with separate pathways having been identified for predator, conspecific and physically harmful threats. In particular, the dorsomedial part of the ventromedial hypothalamus (VHMdm) is critical for the expression of defensive responses to predators. Here, we tested the hypothesis that this circuit also participates in predator fear memory by transient pharmacogenetic inhibition of the VMHdm and its downstream effector, the dorsal periaqueductal grey, during predator fear learning in the mouse. Our data demonstrate that neural activity in the VMHdm is required for both the acquisition and recall of predator fear memory, whereas that of its downstream effector, the dorsal periaqueductal grey, is required only for the acute expression of fear. These findings are consistent with a role for the medial hypothalamus in encoding an internal emotional state of fear. 相似文献
9.
M Heringlake T Kox J Poeling S Klaus T Hanke N Franz F Eberhardt H Heinze FP Armbruster L Bahlmann 《European journal of medical research》2009,14(3):106-112
The insulin-like and vasodilatatory polypeptide relaxin (RLX), formerly known as a pregnancy hormone, has gained interest as a potential humoral mediator in human heart failure. Controversy exists about the relation between plasma levels of RLX and the severity of heart failure. The present study was designed to determine the course of RLX, atrial, and brain natriuretic peptide (NT-proANP and NT-proBNP) during physical exercise in patients with ischemic heart disease (IHD) and to relate hormone levels to peak cardiac power output (CPO) as a measure of cardiopulmonary function with prognostic relevance. 40 patients with IHD were studied during right-heart-catheterization at rest and during supine bicycle ergometry. RLX, NTproBNP, and NTproANP were determined before, during exercise, and after recovery. NT-proANP and NT-proBNP levels increased during maximal charge, and recovery while RLX levels decreased. Cardiac power output at maximal charge correlated inversely with NTproANP and NTproBNP but positively with RLX. Patients with high degree heart failure (CPO < 1.96 W) had higher NTproANP and NTproB-NP and lower RLX levels than patients with low degree heart failure. While confirming the role of NTproANP and NTproBNP as markers for the severity of heart failure, the present data do not support the concept that plasma levels of RLX are related to the severity of myocardial dysfunction and that systemic RLX acts as a compensatory vasodilatatory response hormone in ischemic heart disease. 相似文献
10.
Green N Hu Y Janz K Li HQ Kaila N Guler S Thomason J Joseph-McCarthy D Tam SY Hotchandani R Wu J Huang A Wang Q Leung L Pelker J Marusic S Hsu S Telliez JB Hall JP Cuozzo JW Lin LL 《Journal of medicinal chemistry》2007,50(19):4728-4745
Tumor progression loci-2 (Tpl2) (Cot/MAP3K8) is a serine/threonine kinase in the MAP3K family directly upstream of MEK. Recent studies using Tpl2 knockout mice have indicated an important role for Tpl2 in the lipopolysaccharide (LPS) induced production of tumor necrosis factor alpha (TNF-alpha) and other proinflammatory cytokines involved in diseases such as rheumatoid arthritis. Initial 4-anilino-6-aminoquinoline-3-carbonitrile leads showed poor selectivity for Tpl2 over epidermal growth factor receptor (EGFR) kinase. Using molecular modeling and crystallographic data of the EGFR kinase domain with and without an EGFR kinase-specific 4-anilinoquinazoline inhibitor (erlotinib, Tarceva), we hypothesized that we could diminish the inhibition of EGFR kinase by substitution at the C-8 position of our 4-anilino-6-aminoquinoline-3-carbonitrile leads. The 8-substituted-4-anilino-6-aminoquinoline-3-carbonitriles were prepared from the appropriate 2-substituted 4-nitroanilines. Modifications to the C-6 and C-8 positions led to the identification of compounds with increased inhibition of TNF-alpha release from LPS-stimulated rat and human blood, and these analogues were also highly selective for Tpl2 kinase over EGFR kinase. Further structure-activity based modifications led to the identification of 8-bromo-4-(3-chloro-4-fluorophenylamino)-6-[(1-methyl-1H-imidazol-4-yl)methylamino]quinoline-3-carbonitrile, which demonstrated in vitro as well as in vivo efficacy in inhibition of LPS-induced TNF-alpha production. 相似文献