全文获取类型
收费全文 | 772篇 |
免费 | 59篇 |
国内免费 | 13篇 |
专业分类
耳鼻咽喉 | 9篇 |
儿科学 | 56篇 |
妇产科学 | 12篇 |
基础医学 | 133篇 |
口腔科学 | 13篇 |
临床医学 | 75篇 |
内科学 | 207篇 |
皮肤病学 | 34篇 |
神经病学 | 45篇 |
特种医学 | 37篇 |
外科学 | 85篇 |
综合类 | 28篇 |
一般理论 | 1篇 |
预防医学 | 33篇 |
眼科学 | 8篇 |
药学 | 41篇 |
肿瘤学 | 27篇 |
出版年
2022年 | 4篇 |
2021年 | 5篇 |
2020年 | 12篇 |
2019年 | 9篇 |
2018年 | 16篇 |
2017年 | 17篇 |
2016年 | 23篇 |
2015年 | 14篇 |
2014年 | 24篇 |
2013年 | 44篇 |
2012年 | 46篇 |
2011年 | 39篇 |
2010年 | 31篇 |
2009年 | 41篇 |
2008年 | 46篇 |
2007年 | 33篇 |
2006年 | 35篇 |
2005年 | 32篇 |
2004年 | 22篇 |
2003年 | 25篇 |
2002年 | 16篇 |
2001年 | 23篇 |
2000年 | 25篇 |
1999年 | 6篇 |
1998年 | 21篇 |
1997年 | 22篇 |
1996年 | 23篇 |
1995年 | 18篇 |
1994年 | 11篇 |
1993年 | 17篇 |
1992年 | 8篇 |
1991年 | 8篇 |
1990年 | 6篇 |
1989年 | 13篇 |
1988年 | 14篇 |
1987年 | 7篇 |
1986年 | 11篇 |
1985年 | 7篇 |
1984年 | 4篇 |
1983年 | 8篇 |
1982年 | 5篇 |
1980年 | 6篇 |
1979年 | 4篇 |
1978年 | 4篇 |
1977年 | 6篇 |
1976年 | 4篇 |
1975年 | 4篇 |
1974年 | 8篇 |
1973年 | 3篇 |
1966年 | 2篇 |
排序方式: 共有844条查询结果,搜索用时 0 毫秒
1.
Katharine R. Owen Mollie Donohoe Sian Ellard Andrew T. Hattersley 《Diabetic medicine》2003,20(10):823-827
Background Familial partial lipodystrophy (FPLD) is a monogenic form of diabetes characterised by a dominantly inherited disorder of adipose tissue associated with the loss of subcutaneous fat from the limbs and trunk, with excess fat deposited around the face and neck. The lipodystrophy causes severe insulin resistance, resulting in acanthosis nigricans, diabetes, dyslipidaemia, and increased risk of cardiovascular disease. Preliminary results from animals and man suggest that increasing subcutaneous fat by treatment with thiazolidinediones should improve insulin resistance and the associated features of this syndrome. Case report We report a 24-year-old patient with FPLD caused by a mutation in the LMNA gene (R482W) treated with 12 months of rosiglitazone. Subcutaneous fat increased following rosiglitazone treatment as demonstrated by a 29% generalised increase in skin-fold thickness. Leptin levels increased from 5.8 to 11.2 ng/ml. Compared with treatment on Metformin, there was an increase in insulin sensitivity (HOMA S% 17.2–31.6) but no change in glycaemic control. The lipid profile worsened during the follow-up period. Conclusion This initial case suggests that, for modification of cardiovascular risk factors, there are no clear advantages in treating patients with FPLD with rosiglitazone despite increases in subcutaneous adipose tissue. Larger series will be needed to identify moderate beneficial effects and treatment may be more effective in patients with generalised forms of lipodystrophy. 相似文献
2.
In a series of experiments in which Mongolian gerbils were trained to jump over a variable gap, it was demonstrated that computation of the distance to be jumped was dependent on both image size and retinal motion, the latter cue being generated by the production of vertical translation movements of the head (head bobs). When image size was not a reliable cue, the animals produced more head bobs, thereby increasing the availability of retinal motion cues. The performance of the gerbils on various probe trials strongly suggested that they computed absolute distance by combining information about the velocity (or amplitude) of their head bobs with information about the velocity (or displacement) of the moving image of the landing platform. 相似文献
3.
4.
MY Mancao LJ Sindel PH Richardson FM Silver 《Acta paediatrica (Oslo, Norway : 1992)》1996,85(1):118-120
Croup is an acute infectious illness usually occurring in children; it is characterized by brassy cough and stridor. The main pathogens include mainly parainfluenza and influenza viruses. Recently there have been reports of prolonged croup caused by the herpes simplex viruses. We report two cases of prolonged croup due to herpes simplex types 1 and 2. We also review and summarize the reported pediatric cases of herpetic croup. 相似文献
5.
Thomson KL Gloyn AL Colclough K Batten M Allen LI Beards F Hattersley AT Ellard S 《Human mutation》2003,22(5):417
Maturity-onset diabetes of the young (MODY) resulting from mutations in the glucokinase (GCK) gene accounts for approximately 20% of MODY in the UK. We have performed fluorescent single stranded conformation polymorphism (F-SSCP) analysis or direct sequencing of the GCK gene in 212 patients referred as part of a research cohort or for diagnostic molecular genetic testing. Mutation screening has identified 43 different mutations in 61 individuals, of which 21 are novel. This report details the mutations identified and their associated clinical features. 相似文献
6.
Mazarakis ND Azzouz M Rohll JB Ellard FM Wilkes FJ Olsen AL Carter EE Barber RD Baban DF Kingsman SM Kingsman AJ O'Malley K Mitrophanous KA 《Human molecular genetics》2001,10(19):2109-2121
In this report it is demonstrated for the first time that rabies-G envelope of the rabies virus is sufficient to confer retrograde axonal transport to a heterologous virus/vector. After delivery of rabies-G pseudotyped equine infectious anaemia virus (EIAV) based vectors encoding a marker gene to the rat striatum, neurons in regions distal from but projecting to the injection site, such as the dopaminergic neurons of the substantia nigra pars compacta, become transduced. This retrograde transport to appropriate distal neurons was also demonstrated after delivery to substantia nigra, hippocampus and spinal cord and did not occur when vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped vectors were delivered to these sites. In addition, peripheral administration of rabies-G pseudotyped vectors to the rat gastrocnemius muscle leads to gene transfer in motoneurons of lumbar spinal cord. In contrast the same vector pseudotyped with VSV-G transduced muscle cells surrounding the injection site, but did not result in expression in any cells in the spinal cord. Long-term expression was observed after gene transfer in the nervous system and a minimal immune response which, together with the possibility of non-invasive administration, greatly extends the utility of lentiviral vectors for gene therapy of human neurological disease. 相似文献
7.
Gloyn AL Reimann F Girard C Edghill EL Proks P Pearson ER Temple IK Mackay DJ Shield JP Freedenberg D Noyes K Ellard S Ashcroft FM Gribble FM Hattersley AT 《Human molecular genetics》2005,14(7):925-934
Neonatal diabetes can either remit and hence be transient or else may be permanent. These two phenotypes were considered to be genetically distinct. Abnormalities of 6q24 are the commonest cause of transient neonatal diabetes (TNDM). Mutations in KCNJ11, which encodes Kir6.2, the pore-forming subunit of the ATP-sensitive potassium channel (K(ATP)), are the commonest cause of permanent neonatal diabetes (PNDM). In addition to diabetes, some KCNJ11 mutations also result in marked developmental delay and epilepsy. These mutations are more severe on functional characterization. We investigated whether mutations in KCNJ11 could also give rise to TNDM. We identified the three novel heterozygous mutations (G53S, G53R, I182V) in three of 11 probands with clinically defined TNDM, who did not have chromosome 6q24 abnormalities. The mutations co-segregated with diabetes within families and were not found in 100 controls. All probands had insulin-treated diabetes diagnosed in the first 4 months and went into remission by 7-14 months. Functional characterization of the TNDM associated mutations was performed by expressing the mutated Kir6.2 with SUR1 in Xenopus laevis oocytes. All three heterozygous mutations resulted in a reduction in the sensitivity to ATP when compared with wild-type (IC(50) approximately 30 versus approximately 7 microM, P-value for is all <0.01); however, this was less profoundly reduced than with the PNDM associated mutations. In conclusion, mutations in KCNJ11 are the first genetic cause for remitting as well as permanent diabetes. This suggests that a fixed ion channel abnormality can result in a fluctuating glycaemic phenotype. The multiple phenotypes associated with activating KCNJ11 mutations may reflect their severity in vitro. 相似文献
8.
Chan SL Yew WW Porter JH McAdam KP Allen BW Dickinson JM Ellard GA Mitchison DA 《International journal of antimicrobial agents》1994,3(4):267-274
Bioavailability was measured by rifapentine (RPE) serum concentrations and by the urinary ratio between RPE and creatinine, in specimens obtained 4-50 h after 600 mg RPE preceded by food. The bioavailabilities of RPEs manufactured in China and by a Western manufacturer were similar after a standard English breakfast, and serum concentrations were also similar to those obtained in an earlier Italian study following a complex meal. Although absorption of RPE was unsatisfactory after lipid-rich biscuits or shortbread, absorption after egges and toast was excellent and was nearly as good after a fast-food sandwich. The urinary measure of bioavailability at 26 h appeared as efficient as peak serum estimations at 6, 8 and 26 h. Fast-food sandwiches are being taken before RPE in a current clinical trial of Chinese RPE in Hong Kong. 相似文献
9.
Graham G Dark A Hilary Calvert Robert Grimshaw Christopher Poole Ken Swenerton Stan Kaye Robert Coleman Gordon Jayson Tien Le Susan Ellard Marc Trudeau Paul Vasey Marta Hamilton Terri Cameron Emma Barrett Wendy Walsh Lynn McIntosh Elizabeth A Eisenhauer 《Journal of clinical oncology》2005,23(9):1859-1866
PURPOSE: Liposomal lurtotecan (OSI-211) is a liposomal formulation of the water-soluble topoisomerase I inhibitor lurtotecan (GI147211), which demonstrated superior levels of activity compared with topotecan in preclinical models. We studied two schedules of OSI-211 in a randomized design in relapsed ovarian cancer to identify the more promising of the two schedules for further study. PATIENTS AND METHODS: Eligible patients had measurable epithelial ovarian, fallopian, or primary peritoneal cancer that was recurrent after one or two prior regimens of chemotherapy. Patients were randomly assigned to receive either arm A (OSI-211 1.8 mg/m(2)/d administered by 30-minute intravenous infusion on days 1, 2, and 3 every 3 weeks) or arm B (OSI-211 2.4 mg/m(2)/d administered by 30-minute intravenous infusion on days 1 and 8 every 3 weeks). The primary outcome measure was objective response, which was confirmed by independent radiologic review, and a pick the winner statistical design was used to identify the schedule most likely to be superior. RESULTS: Eighty-one patients were randomized between October 2000 and September 2001. The hematologic toxic effects were greater on arm A than on arm B (grade 4 neutropenia, 51% v 22%, respectively), as was febrile neutropenia (26% v 2.4%, respectively). Of the 80 eligible patients, eight patients (10%) had objective responses; six responders (15.4%; 95% CI, 6% to 30%) were in arm A and two responders (4.9%; 95% CI, 1% to 17%) were in arm B. CONCLUSION: The OSI-211 daily for 3 days intravenous schedule met the statistical criteria to be declared the winner in terms of objective response. This schedule was also associated with more myelosuppression than the schedule of OSI-211 administered in arm B. 相似文献
10.
This review correlates the imaging findings and histological appearances seen in chordomas in a series of patients presenting at our institution, together with a published literature review. A parallel presentation of photographs of imaging findings and microscopic histological findings is made, with the aim being to enhance recognition of this uncommon but clinically significant entity. 相似文献