全文获取类型
收费全文 | 598篇 |
免费 | 48篇 |
国内免费 | 12篇 |
专业分类
耳鼻咽喉 | 6篇 |
儿科学 | 25篇 |
妇产科学 | 1篇 |
基础医学 | 94篇 |
口腔科学 | 10篇 |
临床医学 | 62篇 |
内科学 | 84篇 |
皮肤病学 | 11篇 |
神经病学 | 63篇 |
特种医学 | 23篇 |
外科学 | 95篇 |
综合类 | 20篇 |
一般理论 | 1篇 |
预防医学 | 49篇 |
眼科学 | 7篇 |
药学 | 25篇 |
肿瘤学 | 82篇 |
出版年
2023年 | 4篇 |
2021年 | 19篇 |
2020年 | 13篇 |
2019年 | 13篇 |
2018年 | 15篇 |
2017年 | 10篇 |
2016年 | 10篇 |
2015年 | 8篇 |
2014年 | 11篇 |
2013年 | 28篇 |
2012年 | 25篇 |
2011年 | 29篇 |
2010年 | 21篇 |
2009年 | 25篇 |
2008年 | 32篇 |
2007年 | 37篇 |
2006年 | 23篇 |
2005年 | 31篇 |
2004年 | 23篇 |
2003年 | 20篇 |
2002年 | 19篇 |
2001年 | 12篇 |
2000年 | 11篇 |
1999年 | 16篇 |
1998年 | 12篇 |
1997年 | 12篇 |
1996年 | 3篇 |
1995年 | 7篇 |
1994年 | 3篇 |
1993年 | 9篇 |
1992年 | 8篇 |
1991年 | 8篇 |
1990年 | 9篇 |
1989年 | 10篇 |
1988年 | 11篇 |
1987年 | 14篇 |
1986年 | 5篇 |
1985年 | 7篇 |
1984年 | 10篇 |
1983年 | 3篇 |
1982年 | 3篇 |
1981年 | 5篇 |
1980年 | 4篇 |
1977年 | 3篇 |
1976年 | 4篇 |
1975年 | 5篇 |
1973年 | 4篇 |
1971年 | 6篇 |
1969年 | 5篇 |
1966年 | 3篇 |
排序方式: 共有658条查询结果,搜索用时 15 毫秒
11.
Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation 总被引:22,自引:1,他引:22
Marsh DJ; Coulon V; Lunetta KL; Rocca-Serra P; Dahia PL; Zheng Z; Liaw D; Caron S; Duboue B; Lin AY; Richardson AL; Bonnetblanc JM; Bressieux JM; Cabarrot-Moreau A; Chompret A; Demange L; Eeles RA; Yahanda AM; Fearon ER; Fricker JP; Gorlin RJ; Hodgson SV; Huson S; Lacombe D; Eng C 《Human molecular genetics》1998,7(3):507-515
The tumour suppressor gene PTEN , which maps to 10q23.3 and encodes a 403
amino acid dual specificity phosphatase (protein tyrosine phosphatase;
PTPase), was shown recently to play a broad role in human malignancy.
Somatic PTEN deletions and mutations were observed in sporadic breast,
brain, prostate and kidney cancer cell lines and in several primary tumours
such as endometrial carcinomas, malignant melanoma and thyroid tumours. In
addition, PTEN was identified as the susceptibility gene for two hamartoma
syndromes: Cowden disease (CD; MIM 158350) and Bannayan-Zonana (BZS) or
Ruvalcaba-Riley-Smith syndrome (MIM 153480). Constitutive DNA from 37 CD
families and seven BZS families was screened for germline PTEN mutations.
PTEN mutations were identified in 30 of 37 (81%) CD families, including
missense and nonsense point mutations, deletions, insertions, a
deletion/insertion and splice site mutations. These mutations were
scattered over the entire length of PTEN , with the exception of the first,
fourth and last exons. A 'hot spot' for PTEN mutation in CD was identified
in exon 5 that contains the PTPase core motif, with 13 of 30 (43%) CD
mutations identified in this exon. Seven of 30 (23%) were within the core
motif, the majority (five of seven) of which were missense mutations,
possibly pointing to the functional significance of this region. Germline
PTEN mutations were identified in four of seven (57%) BZS families studied.
Interestingly, none of these mutations was observed in the PTPase core
motif. It is also worthy of note that a single nonsense point mutation,
R233X, was observed in the germline DNA from two unrelated CD families and
one BZS family. Genotype-phenotype studies were not performed on this small
group of BZS families. However, genotype-phenotype analysis inthe group of
CD families revealed two possible associations worthy of follow-up in
independent analyses. The first was an association noted in the group of CD
families with breast disease. A correlation was observed between the
presence/absence of a PTEN mutation and the type of breast involvement
(unaffected versus benign versus malignant). Specifically and more
directly, an association was also observed between the presence of a PTEN
mutation and malignant breast disease. Secondly, there appeared to be an
interdependent association between mutations upstream and within the PTPase
core motif, the core motif containing the majority of missense mutations,
and the involvement of all major organ systems (central nervous system,
thyroid, breast, skin and gastrointestinal tract). However, these
observations would need to be confirmed by studying a larger number of CD
families.
相似文献
12.
Wagner Abram L. Porth Julia M. Wu Zhenke Boulton Matthew L. Finlay Jessica M. Kobayashi Lindsay C. 《Journal of community health》2022,47(3):408-415
Journal of Community Health - It is important to distinguish between apprehensions that lead to vaccine rejection and those that do not. In this study, we (1) identifed latent classes of... 相似文献
13.
Irving Lutsky Margaret Hopwood Stephen E. Abram James M. Cerletty Raymond G. Hoffman John P. Kampine 《Journal canadien d'anesthésie》1994,41(7):561-567
In order to determine the prevalence of psychoactive substance use in three specialty groupings, 1,624 questionnaires were sent to physicians in medicine, surgery and anaesthesia; all had trained at the same academic institution. A response rate of 57.8% was achieved. Comparison of prevalence of impairment rates showed no differences between Surgery (14.4%), Medicine (19.9%) and Anaesthesia (16.8%). Substance abuse was clearly associated with a family history of abuse; 32.1% of the abusers had a family history of such abuse compared with 11.7% of the non-abusers. Increased stress at various career stages did not appear to increase substance abuse; problem areas during medical life times were similar for each specialty. Substances most frequently used were marijuana (54.7%), amphetamines (32.9%); and benzodiazepines (25.1%). Seventy-three used psychoactive drugs which were non-prescribed. Drug counselling programmes were judged inadequate by most. Use of alcohol and drugs by faculty members was reported by a number of respondents. 相似文献
14.
MW Lieberman R Barrios G Kala SV Kala ED Lykissa CN Ou 《Environmental health perspectives》1999,107(9):A444-A445
Respond on comments on Lieberman's article: Cyclosiloxanes Produce Fatal Liver and Lung Damage in Mice. Environ Health Perspect 107:161-165 相似文献
15.
Genetic manipulation of mammary epithelium by transplantation 总被引:2,自引:0,他引:2
Genes can be introduced into mammary epitheliumin vivo by the tissue reconstitution method. Primary cultures of mammary epithelial cells are prepared, a gene introduced using retrovirus vectors, and the cells transplanted into a mammary fat pad from which the normal epithelium has been removed. The cells reform an epithelium in which some cells express the introduced gene. The technique is reviewed and compared with the mammary-specific expression of genes in transgenic mice. To model the development of neoplasia, particularly the preneoplastic changes caused by a single oncogene alone, several oncogenes have been expressed this way—myc, Ha-ras, erbB, erbB2,Wnt-1, andhst/FGF-4. Each caused a different alteration to the growth pattern of the epithelium, such as altered branching, premature alveolus development, distorted duct structure, or altered hormone sensitivity. Insights into normal development have also been obtained by inappropriate expression of genes such asWnt-4. 相似文献
16.
17.
Tessa Timmers Rik Ossenkoppele Denise Visser Hayel Tuncel Emma E Wolters Sander CJ Verfaillie Wiesje M van der Flier Ronald Boellaard Sandeep SV Golla Bart NM van Berckel 《Journal of cerebral blood flow and metabolism》2020,40(12):2464
The aim of this study was to investigate the test–retest (TRT) repeatability of various parametric quantification methods for [18F]Flortaucipir positron emission tomography (PET). We included eight subjects with dementia or mild cognitive impairment due to Alzheimer’s disease and six cognitively normal subjects. All underwent two 130-min dynamic [18F]Flortaucipir PET scans within 3 ± 1 weeks. Data were analyzed using reference region models receptor parametric mapping (RPM), simplified reference tissue method 2 (SRTM2) and reference logan (RLogan), as well as standardized uptake value ratios (SUVr, time intervals 40–60, 80–100 and 110–130 min post-injection) with cerebellar gray matter as reference region. We obtained distribution volume ratio or SUVr, first for all brain regions and then in three tau-specific regions-of-interest (ROIs). TRT repeatability (%) was defined as |retest–test|/(average (test + retest)) × 100. For all methods and across ROIs, TRT repeatability ranged from (median (IQR)) 0.84% (0.68–2.15) to 6.84% (2.99–11.50). TRT repeatability was good for all reference methods used, although semi-quantitative models (i.e. SUVr) performed marginally worse than quantitative models, for instance TRT repeatability of RPM: 1.98% (0.78–3.58) vs. SUVr80–100: 3.05% (1.28–5.52), p < 0.001. Furthermore, for SUVr80–100 and SUVr110–130, with higher average SUVr, more variation was observed. In conclusion, while TRT repeatability was good for all models used, quantitative methods performed slightly better than semi-quantitative methods. 相似文献
18.
19.
Reda T Plugge CM Abram NJ Hirst J 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(31):10654-10658
Carbon dioxide (CO2) is a kinetically and thermodynamically stable molecule. It is easily formed by the oxidation of organic molecules, during combustion or respiration, but is difficult to reduce. The production of reduced carbon compounds from CO2 is an attractive proposition, because carbon-neutral energy sources could be used to generate fuel resources and sequester CO2 from the atmosphere. However, available methods for the electrochemical reduction of CO2 require excessive overpotentials (are energetically wasteful) and produce mixtures of products. Here, we show that a tungsten-containing formate dehydrogenase enzyme (FDH1) adsorbed to an electrode surface catalyzes the efficient electrochemical reduction of CO2 to formate. Electrocatalysis by FDH1 is thermodynamically reversible—only small overpotentials are required, and the point of zero net catalytic current defines the reduction potential. It occurs under thoroughly mild conditions, and formate is the only product. Both as a homogeneous catalyst and on the electrode, FDH1 catalyzes CO2 reduction with a rate more than two orders of magnitude faster than that of any known catalyst for the same reaction. Formate oxidation is more than five times faster than CO2 reduction. Thermodynamically, formate and hydrogen are oxidized at similar potentials, so formate is a viable energy source in its own right as well as an industrially important feedstock and a stable intermediate in the conversion of CO2 to methanol and methane. FDH1 demonstrates the feasibility of interconverting CO2 and formate electrochemically, and it is a template for the development of robust synthetic catalysts suitable for practical applications. 相似文献
20.
Enhanced thromboxane synthesis during chronic reductions in uterine perfusion pressure in pregnant rats 总被引:1,自引:0,他引:1
Llinás MT Alexander BT Seedek M Abram SR Crell A Granger JP 《American journal of hypertension》2002,15(9):793-797
BACKGROUND: The purpose of this study was to determine the role of thromboxane A2 (TXA2) in a conscious, chronically instrumented rat model of pregnancy-induced hypertension (PIH) produced by chronic reductions in uterine perfusion pressure (RUPP). METHODS: Mean arterial pressure (MAP), glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and 24-h urinary excretion of TXB2 (metabolite of TXA2) were determined in normal pregnant rats and RUPP pregnant rats. RESULTS: At day 20 of pregnancy, RUPP rats showed a significantly (P < .05) higher MAP (125 +/- 3 mm Hg v 100 +/- 2 mm Hg) as compared with normal pregnant controls. The elevation in arterial pressure in RUPP group was associated with a marked increase (P < .05) in the urinary concentration of TXB2 compared with normal pregnant group (3663 +/- 488 v 2646 +/- 257 pg/24 h). Baseline GFR (1.74 +/- 0.13 v 2.40 +/- 0.20 mL/min, respectively, P < .05) and ERPF (5.13 +/- 0.44 v 6.44 +/- 0.58 mL/min, respectively) were decreased in RUPP rats relative to pregnant controls. Infusion of a TX receptor antagonist, SQ 29,548 (2 mg/kg bolus plus 2 mg/kg per h infusion) had no significant effect on increased MAP in RUPP pregnant rats. Similarly, ERPF and GFR did not change during acute blockade of TXA2 receptors in this group. CONCLUSION: These findings suggest that enhanced production of TXA2 does not play a major role in mediating the hypertension and renal vasoconstriction produced by chronic RUPP in pregnant rats. 相似文献