全文获取类型
收费全文 | 203篇 |
免费 | 69篇 |
国内免费 | 1篇 |
专业分类
妇产科学 | 3篇 |
基础医学 | 33篇 |
临床医学 | 56篇 |
内科学 | 117篇 |
皮肤病学 | 2篇 |
神经病学 | 13篇 |
特种医学 | 1篇 |
外科学 | 29篇 |
综合类 | 1篇 |
一般理论 | 2篇 |
预防医学 | 2篇 |
眼科学 | 4篇 |
药学 | 5篇 |
肿瘤学 | 5篇 |
出版年
2023年 | 3篇 |
2022年 | 2篇 |
2021年 | 9篇 |
2020年 | 3篇 |
2019年 | 4篇 |
2018年 | 2篇 |
2016年 | 3篇 |
2015年 | 4篇 |
2014年 | 3篇 |
2013年 | 5篇 |
2012年 | 13篇 |
2011年 | 6篇 |
2010年 | 9篇 |
2009年 | 7篇 |
2008年 | 13篇 |
2007年 | 11篇 |
2006年 | 14篇 |
2005年 | 9篇 |
2004年 | 11篇 |
2003年 | 6篇 |
2002年 | 6篇 |
2001年 | 9篇 |
2000年 | 16篇 |
1999年 | 11篇 |
1998年 | 7篇 |
1997年 | 4篇 |
1996年 | 5篇 |
1995年 | 8篇 |
1993年 | 2篇 |
1992年 | 4篇 |
1991年 | 4篇 |
1989年 | 4篇 |
1988年 | 3篇 |
1987年 | 3篇 |
1986年 | 4篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1981年 | 2篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1976年 | 5篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1968年 | 1篇 |
1966年 | 1篇 |
1937年 | 1篇 |
1936年 | 6篇 |
1935年 | 9篇 |
1934年 | 7篇 |
1932年 | 1篇 |
排序方式: 共有273条查询结果,搜索用时 15 毫秒
1.
A Coagulation Factor IX-Deficient Mouse Model for Human Hemophilia B 总被引:25,自引:10,他引:15
Lin Hui-Feng; Maeda Nobuyo; Smithies Oliver; Straight David L.; Stafford Darrel W. 《Blood》1997,90(10):3962-3966
2.
Targeted gene duplication and disruption for analyzing quantitative genetic traits in mice. 总被引:16,自引:3,他引:13 下载免费PDF全文
O Smithies H S Kim 《Proceedings of the National Academy of Sciences of the United States of America》1994,91(9):3612-3615
Experimental analysis of complex quantitative genetic traits, such as essential hypertension, should be greatly facilitated by being able to manipulate the expression of a gene in living animals without altering the nucleotide sequence, chromosomal location, or regulatory elements of the gene. To explore this possibility, we have used targeted gene disruption and duplication to generate mice that are genetically identical [(129 x C57BL6)F1] except for having one, two, or three functional copies of the gene coding for angiotensinogen. The two-copy animals have two normal copies of the angiotensinogen gene; the one-copy and three-copy animals have one normal copy with the other either disrupted or duplicated by gene targeting. The duplicated pair of genes was generated by a special form of gap-repair gene targeting that tandemly duplicates the whole of a gene together with 5' and 3' flanking regions. We find progressively and significantly higher levels of the gene product in the animals having increasing numbers of gene copies: the one-copy animals have steady-state plasma angiotensinogen levels approximately 35% of normal (P < 0.0001), and the three-copy animals have levels approximately 124% of normal (P < 0.004). Detailed information about regulatory sequences is not required for this type of experiment; nor is it necessary to have DNA clones or targeting constructs that cover the whole of the target gene. Varying gene copy numbers by targeting consequently offers a promising approach to quantitative genetics. 相似文献
3.
4.
McLennan NF Brennan PM McNeill A Davies I Fotheringham A Rennison KA Ritchie D Brannan F Head MW Ironside JW Williams A Bell JE 《The American journal of pathology》2004,165(1):227-235
The function of the normal conformational isoform of prion protein, PrP(C), remains unclear although lines of research have suggested a role in the cellular response to oxidative stress. Here we investigate the expression of PrP(C) in hypoxic brain tissues to examine whether PrP(C) is in part regulated by neuronal stress. Cases of adult cerebral ischemia and perinatal hypoxic-ischemic injury in humans were compared with control tissues. PrP(C) immunoreactivity accumulates within neuronal processes in the penumbra of hypoxic damage in adult brain, and within neuronal soma in cases of perinatal hypoxic-ischemic injury, and in situ hybridization analysis suggests an up-regulation of PrP mRNA during hypoxia. Rodents also showed an accumulation of PrP(C) in neuronal soma within the penumbra of ischemic lesions. Furthermore, the infarct size in PrP-null mice was significantly greater than in the wild type, supporting the proposed role for PrP(C) in the neuroprotective adaptive cellular response to hypoxic injury. 相似文献
5.
Katharine Edgerley Lisa Bryson Lucy Hanington Rachel Irving Shelagh Joss Anne Lampe Isabelle Maystadt Deborah Osio Ruth Richardson Miranda Split Francis H. Sansbury Ingrid Scurr Helen Stewart Alisdair McNeil Karen Low 《American journal of medical genetics. Part A》2023,191(5):1447-1458
To delineate further the clinical phenotype of Lamb–Shaffer Syndrome (LSS) 16 unpublished patients with heterozygous variation in SOX5 were identified either through the UK Decipher database or the study team was contacted by clinicians directly. Clinical phenotyping tables were completed for each patient by their responsible clinical geneticist. Photos and clinical features were compared to assess key phenotypes and genotype–phenotype correlation. We report 16 SOX5 variants all of which meet American College of Medical Genetics/Association for Clinical Genomic Science ACMG/ACGS criteria class IV or V. 7/16 have intragenic deletions of SOX5 and 9/16 have single nucleotide variants (including both truncating and missense variants). The cohort includes two sets of monozygotic twins and parental gonadal mosaicism is noted in one family. This cohort of 16 patients is compared with the 71 previously reported cases and corroborates previous phenotypic findings. As expected, the most common findings include global developmental delay with prominent speech delay, mild to moderate intellectual disability, behavioral abnormalities and sometimes subtle characteristic facial features. We expand in more detail on the behavioral phenotype and observe that there is a greater tendency toward lower growth parameters and microcephaly in patients with single nucleotide variants. This cohort provides further evidence of gonadal mosaicism in SOX5 variants; this should be considered when providing genetic counseling for couples with one affected child and an apparently de novo variant. 相似文献
6.
Gene targeting approaches to complex genetic diseases: atherosclerosis and essential hypertension. 总被引:10,自引:3,他引:7 下载免费PDF全文
O Smithies N Maeda 《Proceedings of the National Academy of Sciences of the United States of America》1995,92(12):5266-5272
Gene targeting allows precise, predetermined changes to be made in a chosen gene in the mouse genome. To date, targeting has been used most often for generation of animals completely lacking the product of a gene of interest. The resulting "knockout" mice have confirmed some hypotheses, have upset others, but have rarely been uninformative. Models of several human genetic diseases have been produced by targeting--including Gaucher disease, cystic fibrosis, and the fragile X syndrome. These diseases are primarily determined by defects in single genes, and their modes of inheritance are well understood. When the disease under study has a complex etiology with multiple genetic and environmental components, the generation of animal models becomes more difficult but no less valuable. The problems associated with dissecting out the individual genetic factors also increases substantially and the distinction between causation and correlation is often difficult. To prove causation in a complex system requires rigorous adherence to the principle that the experiments must allow detection of the effects of changing only a single variable at one time. Gene targeting experiments, when properly designed, can test the effects of a precise genetic change completely free from the effects of differences in any other genes (linked or unlinked to the test gene). They therefore allow proofs of causation. 相似文献
7.
Derek J. Smithies Philip H. Butler W. Antony Day E. Peter Walker 《Lasers in medical science》1995,10(2):93-104
This paper reports the electron microscopy results obtained from two patients who were treated with 5 W of yellow (578 nm) light from a copper vapour laser with an illumination time of 3.6 ms and a 0.3 mm spot diameter. The endpoint of treatment was transient blanching. Following treatment, erythema was observed. There was minimal damage to the epidermis and non-vascular tissue such as the nerve fibres. There was severe damage to the endothelial cells of the ectatic vessels. Twenty-four hours after treatment, platelet activation and collagen were present, indicating that these vessels were no longer viable. Theoretical calculations are used to determine the flow of heat within and away from a 50m diameter vessel. From this, heating of the entire vessel is shown to occur with illumination times of 4 ms, with minimal heating of the non-vascular tissue. Shorter illuminations do not heat the entire vessel, while the use of longer illumination times will cause excessive damage to the surrounding non-vascular tissue. Illumination times close to 4 ms must be regarded as optimal. 相似文献
8.
Craig N. Parnaby Alisdair J. MacDonald John T. Jenkins 《International journal of colorectal disease》2009,24(5):585-592
Purpose Enhanced recovery programs aim to expedite gut function after elective colorectal surgery. Early oral feeding simulates gut
function but is not always feasible. Gum chewing, a form of sham feed, is an alternative. We assessed current evidence for
gum chewing and gut function.
Study design All randomized controlled trials (RCTs) between 1990 and 2008 comparing gum chewing with controls/placebo were analyzed irrespective
of language, blinding, or publication bias. The Jadad scale was used to assess study quality. Endpoints were time to flatus/feces,
postoperative complications, and hospital stay. Random and fixed models were employed to aggregate study endpoints and assess
heterogeneity.
Results Six RCTs containing 256 patients were included. Significant heterogeneity was identified and random effects model was employed.
Heterogeneity may be explained through variations in delivery of surgical care. Significant reductions in the time to flatus
and time to feces were identified but no significant difference in hospital or in-hospital postoperative complications were
found.
Conclusions Gum chewing significantly reduced time to flatus and feces; however, hospital stay and postoperative complications were not
reduced. Significant study heterogeneity means that these results should be interpreted with caution.
Presentation to European Society of Coloproctology Annual Scientific Meeting Malta September 2007
Presentation to West of Scotland Surgical Association Annual Scientific Meeting October 2007 相似文献
9.
Assessment of endoscopic retrograde cholangio-pancreatography (ERCP) and pure pancreatic juice cytology in patients with pancreatic disease. 下载免费PDF全文
Pure pancreatic juice has been collected from 61 patients at the time of endoscopic retrograde cholangio-pancreatography (ERCP) for the purpose of cytodiagnosis. The ERCP and cytological findings are discussed. Pure pancreatic juice cytology may help in the interpretation of the pancreatogram in both pancreatitis and pancreatic carcinoma. In patients with pancreatic carcinoma, ERCP alone was diagnostic in 65%, cytology alone in 54%. By combining these two approaches, a diagnostic result was obtained in 92% of patients. 相似文献
10.
Mohamed A. Salem Rasha Ali Radwan Eman Sherien Mostafa Saleh Alseekh Alisdair R. Fernie Shahira M. Ezzat 《RSC advances》2020,10(52):31511
Aging is an unavoidable fate that afflicts all life, during this process in mammals reactive oxygen species (ROS) are generated which stimulate tyrosinase, elastase and collagenase activities that actively participate in skin aging. Therefore, the maintenance of antioxidant homeostasis is an important anti-aging strategy for skin. Nature has excellent anti-aging remedies that act externally as well as internally to delay the visual signs of aging. In view of this fact, the present study investigates the in vitro anti-aging activity of five medicinal plants belonging to phenolic rich families namely Rosmarinus officinalis, Lavandula officinalis, Matricaria chamomilla, Camellia sinensis and Pelargonium graveolens. The selected plants are those most frequently used in the preparation of ethnomedicinal recipes for the prevention or treatment of aging. The inhibitory effects of the ethanolic and aqueous extracts of the five selected plants on the activity of tyrosinase, elastase, and collagenase enzymes were investigated. Furthermore, the chemical composition of the plants and the antioxidant capacity of their extracts were assessed. The results showed that R. officinalis had the highest total phenolics content which was correlated with its potent antioxidant and anti-aging activities. To pinpoint the active metabolites in the tested extracts, we evaluated the metabolite variations using ultra-performance liquid chromatography coupled with high resolution electrospray ionization-tandem mass spectrometry (UPLC-HR-ESI-MS/MS). Multivariate data analysis (MVDA) revealed that R. officinalis significantly accumulated metabolites from the aromatic diterpenoid, flavonoid and phenolic acid classes. These results indicate that rosemary can be used for further development of topical preparations with anti-aging properties.Aging is an unavoidable fate that afflicts all life, during this process in mammals, reactive oxygen species (ROS) are generated which stimulate tyrosinase, elastase and collagenase activities that actively participate in skin aging. 相似文献