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81.
Association of the steroid synthesis gene CYP11a with polycystic ovary syndrome and hyperandrogenism 总被引:12,自引:0,他引:12
Gharani N; Waterworth DM; Batty S; White D; Gilling-Smith C; Conway GS; McCarthy M; Franks S; Williamson R 《Human molecular genetics》1997,6(3):397-402
Biochemical data implicate an underlying disorder of androgen biosynthesis
and/or metabolism in the aetiology of polycystic ovary syndrome (PCOS). We
have examined the segregation of the genes coding for two key enzymes in
the synthesis and metabolism of androgens, cholesterol side chain cleavage
(CYP11a) and aromatase (CYP19), with PCOS in 20 multiply-affected families.
All analyses excluded CYP19 cosegregation with PCOS, demonstrating that
this locus is not a major determinant of risk for the syndrome. However,
our results provide evidence for linkage to the CYP11a locus (NPL score =
3.03, p = 0.003). Parametric analysis using a dominant model suggests
genetic heterogeneity, generating a maximum HLOD score of 2.7 (alpha =
0.63). An association study of 97 consecutively identified Europids with
PCOS and matched controls demonstrates significant allelic association of a
CYP11a 5' UTR pentanucleotide repeat polymorphism with hirsute PCOS
subjects (p = 0.03). A strong association was also found between alleles of
this polymorphism and total serum testosterone levels in both affected and
unaffected individuals (p = 0.002). Our data demonstrate that variation in
CYP11a may play an important role in the aetiology of hyperandrogenaemia
which is a common characteristic of polycystic ovary syndrome.
相似文献
82.
MD Ronghe ABM Foot R Martin M Ashworth CG Steward 《Acta paediatrica (Oslo, Norway : 1992)》2001,90(5):584-586
Barth syndrome is a metabolic disease characterized by infantile cardiomyopathy, neutropenia and organic aciduria. We report disease evolution in one of the first affected boys to undergo successful cardiac transplantation. CONCLUSION: Although cardiac status stabilized, he developed disabling skeletal myopathy, protracted lymphopenia and--5 y after transplant--fatal Epstein Barr (EBV)-negative T-cell non-Hodgkin's lymphoma. 相似文献
83.
R E Hind M Loizidou J Fleming V Batty S Birch I Taylor 《European journal of surgical oncology》1992,18(2):162-167
Lipiodol, a derivative of poppy seed oil, has been used angiographically to improve visualisation of small liver tumours. We have utilised this finding to determine whether intrahepatic arterial injection of lipiodol can be used as a vehicle to deliver selectively 131I into liver tumours. Two groups of rats were studied. Group 1 (control, no liver tumour) received 0.1 ml 131I-lipiodol (1 microCi) into the hepatic artery. Animals were killed at regular time intervals over 30 days and organs were submitted to well-counting. Over 90% of activity remained in the liver at 6 h. Eighty per cent activity was lost from the normal liver, to be excreted in the urine over 30 days. Group 2 animals received intraportal injections of 7.5 x 10(5) MC28 sarcoma cells. Multiple liver metastases were present after 14 days. Animals were similarly studied at each time interval and samples from tumour and normal liver were submitted to well-counting. Lipiodol was selectively retained within tumour and cleared from normal liver. 131I-lipiodol may prove valuable as a delivery agent for radio/chemotherapy to liver metastases. 相似文献
84.
Hajduch E Balendran A Batty IH Litherland GJ Blair AS Downes CP Hundal HS 《Diabetologia》2001,44(2):173-183
Aims/hypothesis. Increased cellular production of ceramide has been implicated in the pathogenesis of insulin resistance and in the impaired
utilisation of glucose. In this study we have used L6 muscle cells to investigate the mechanism by which the short-chain ceramide
analogue, C2-ceramide, promotes a loss in insulin sensitivity leading to a reduction in insulin stimulated glucose transport and glycogen
synthesis. Method. L6 muscle cells were pre-incubated with C2-ceramide and the effects of insulin on glucose transport, glycogen synthesis and the activities of key molecules involved
in proximal insulin signalling determined. Results. Incubation of L6 muscle cells with ceramide (100 μmol/l) for 2 h led to a complete loss of insulin-stimulated glucose transport
and glycogen synthesis. This inhibition was not due to impaired insulin receptor substrate 1 phosphorylation or a loss in
phosphoinositide 3-kinase activation but was caused by a failure to activate protein kinase B. This defect could not be attributed
to inhibition of 3-phosphoinositide-dependent kinase-1, or to impaired binding of phosphatidylinositol 3,4,5 triphosphate
(PtdIns(3,4,5)P3) to the PH domain of protein kinase B, but results from the inability to recruit protein kinase B to the plasma membrane.
Expression of a membrane-targetted protein kinase B led to its constitutive activation and an increase in glucose transport
that was not inhibited by ceramide. Conclusions/interpretation. These findings suggest that a defect in protein kinase B recruitment underpins the ceramide-induced loss in insulin sensitivity
of key cell responses such as glucose transport and glycogen synthesis in L6 cells. They also suggest that a stimulated rise
in PtdIns(3,4,5)P3 is necessary but not sufficient for protein kinase B activation in this system. [Diabetologia (2001) 44: 173–183]
Received: 5 May 2000 and in revised form: 30 October 2000 相似文献
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89.
HM Badland M Oliver RA Kearns S Mavoa K Witten MJ Duncan GD Batty 《Social science & medicine (1982)》2012,75(8):1469-1476
Although the neighbourhoods and health field is well established, the relationships between neighbourhood selection, neighbourhood preference, work-related travel behaviours, and transport infrastructure have not been fully explored. It is likely that understanding these complex relationships more fully will inform urban policy development, and planning for neighbourhoods that support health behaviours. Accordingly, the objective of this study was to identify associations between these variables in a sample of employed adults. Self-reported demographic, work-related transport behaviours, and neighbourhood preference data were collected from 1616 employed adults recruited from 48 neighbourhoods located across four New Zealand cities. Data were collected between April 2008 and September 2010. Neighbourhood built environment measures were generated using geographical information systems. Findings demonstrated that more people preferred to live in urban (more walkable), rather than suburban (less walkable) settings. Those living in more suburban neighbourhoods had significantly longer work commute distances and lower density of public transport stops available within the neighbourhood when compared with those who lived in more urban neighbourhoods. Those preferring a suburban style neighbourhood commuted approximately 1.5 km further to work when compared with participants preferring urban settings. Respondents who preferred a suburban style neighbourhood were less likely to take public or active transport to/from work when compared with those who preferred an urban style setting, regardless of the neighbourhood type in which they resided. Although it is unlikely that constructing more walkable environments will result in work-related travel behaviour change for all, providing additional highly walkable environments will help satisfy the demand for these settings, reinforce positive health behaviours, and support those amenable to change to engage in higher levels of work-related public and active transport. 相似文献
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