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991.
992.
A mono-sited transferrin from a representative deuterostome: the ascidian Pyura stolonifera (subphylum Urochordata) 总被引:4,自引:0,他引:4
An iron-binding protein has been found in the plasma of Pyura stolonifera. This protein has a molecular weight of about 41,000 +/- 2,000 and binds 1 mol iron/mol protein. The absorption maxima are lambda = 280 and lambda = 429 nm (E429/E280 = 0.044). Bicarbonate is bound concomitantly with high affinity and is necessary for optimal color formation at lambda = 429 nm. The protein showed a negligible exchange of iron with human apotransferrin under physiologic conditions over two hours. Upon incubation with rat reticulocytes, the protein reacts with membrane receptors for transferrins, and the protein, with its iron, is transported intracellularly where the iron is incorporated into heme. The 59Fe protein, after intravenous injection, disappears rapidly from the plasma and is excreted largely in the urine, with a substantial fraction present in the kidney and another large fraction present in the gut. These findings established the protein as a "transferrin" and support the concept that the larger transferrin molecule in vertebrates, with two iron-binding sites, resulted from a gene duplication. 相似文献
993.
Truncated N-terminal fragments of huntingtin with expanded glutamine repeats form nuclear and cytoplasmic aggregates in cell culture 总被引:11,自引:12,他引:11
Cooper JK; Schilling G; Peters MF; Herring WJ; Sharp AH; Kaminsky Z; Masone J; Khan FA; Delanoy M; Borchelt DR; Dawson VL; Dawson TM; Ross CA 《Human molecular genetics》1998,7(5):783-790
Huntington's disease (HD) is a progressive neurodegenerative disorder
caused by an expanding CAG repeat coding for polyglutamine in the
huntingtin protein. Recent data have suggested the possibility that an
N-terminal fragment of huntingtin may aggregate in neurons of patients with
HD, both in the cytoplasm, forming dystrophic neurites, and in the nucleus,
forming intranuclear neuronal inclusion bodies. An animal model of HD using
the short N-terminal fragment of huntingtin has also been found to have
intranuclear inclusions and this same fragment can aggregate in vitro . We
have now developed a cell culture model demonstrating that N-terminal
fragments of huntingtin with expanded glutamine repeats aggregate both in
the cytoplasm and in the nucleus. Neuroblastoma cells transiently
transfected with full-length huntingtin constructs with either a normal or
expanded repeat had diffuse cytoplasmic localization of the protein. In
contrast, cells transfected with truncated N-terminal fragments showed
aggregation only if the glutamine repeat was expanded. The aggregates were
often ubiquitinated. The shorter truncated product appeared to form more
aggregates in the nucleus. Cells transfected with the expanded repeat
construct but not the normal repeat construct showed enhanced toxicity to
the apoptosis- inducing agent staurosporine. These data indicate that
N-terminal truncated fragments of huntingtin with expanded glutamine
repeats can aggregate in cells in culture and that this aggregation can be
toxic to cells. This model will be useful for future experiments to test
mechanisms of aggregation and toxicity and potentially for testing
experimental therapeutic interventions.
相似文献
994.
Nestorowicz A; Glaser B; Wilson BA; Shyng SL; Nichols CG; Stanley CA; Thornton PS; Permutt MA 《Human molecular genetics》1998,7(7):1119-1128
Familial hyperinsulinism (HI) is a disorder characterized by dysregulation
of insulin secretion and profound hypoglycemia. Mutations in both the
Kir6.2 and sulfonylurea receptor (SUR1) genes have been associated with the
autosomal recessive form of this disorder. In this study, the spectrum and
frequency of SUR1 mutations in HI and their significance to clinical
manifestations of the disease were investigated by screening 45 HI probands
of various ethnic origins for mutations in the SUR1 gene. Single-strand
conformation polymorphism (SSCP) and nucleotide sequence analyses of
genomic DNA revealed a total of 17 novel and three previously described
mutations in SUR1 . The novel mutations comprised one nonsense and 10
missense mutations, two deletions, three mutations in consensus splice-site
sequences and an in- frame insertion of six nucleotides. One mutation
occurred in the first nucleotide binding domain (NBF-1) of the SUR1
molecule and another eight mutations were located in the second nucleotide
binding domain (NBF-2), including two at highly conserved amino acid
residues within the Walker A sequence motif. The majority of the remaining
mutations was distributed throughout the three putative transmembrane
domains of the SUR1 protein. With the exception of the 3993-9G-->A
mutation, which was detected on 4.5% (4/88) disease chromosomes, allelic
frequencies for the identified mutations varied between 1.1 and 2.3% for HI
chromosomes, indicating that each mutation was rare within the patient
cohort. The clinical manifestations of HI in those patients homozygous for
mutations in the SUR1 gene are described. In contrast with the allelic
homogeneity of HI previously described in Ashkenazi Jewish patients, these
findings suggest that a large degree of allelic heterogeneity at the SUR1
locus exists in non-Ashkenazi HI patients. These data have important
implications for genetic counseling and prenatal diagnosis of HI, and also
provide a basis to further elucidate the molecular mechanisms underlying
the pathophysiology of this disease.
相似文献
995.
996.
997.
Measured haplotype analysis of the angiotensin-I converting enzyme gene 总被引:20,自引:5,他引:20
Keavney B; McKenzie CA; Connell JM; Julier C; Ratcliffe PJ; Sobel E; Lathrop M; Farrall M 《Human molecular genetics》1998,7(11):1745-1751
Linkage and segregation analysis have shown that circulating angiotensin-I
converting enzyme (ACE) levels are influenced by a major quantitative trait
locus that maps within or close to the ACE gene. The D variant of a 287 bp
insertion/deletion (I/D) polymorphism in intron 16 of the gene is
associated with high ACE levels and may also be related to increased risk
of cardiovascular disease. Multiple variants that are in linkage
disequilibrium with the I/D polymorphism have been described, but it is
unknown if any of these are directly implicated, alone or in combination
with as yet undiscovered variants, in the determination of ACE levels. An
analysis of 10 polymorphisms spanning 26 kb of the ACE gene revealed a
limited number of haplotypes in Caucasian British families due to strong
linkage disequilibrium operating over this small chromosomal region. A
haplotype tree (cladogram) was constructed with three main branches (clades
A-C) which account for 90% of the observed haplotypes. Clade C is most
likely derived from clades A and B following an ancestral recombination
event. This evolutionary information was then used to direct a series of
nested, measured haplotype analyses that excluded upstream sequences,
including the ACE promoter, from harbouring the major ACE-linked variant
that explains 36% of the total trait variability. Residual familial
correlations were highly significant, suggesting the influence of
additional unlinked genes. Our results demonstrate that a combined
cladistic/measured haplotype analysis of polymorphisms within a gene
provides a powerful means to localize variants that directly influence a
quantitative trait.
相似文献
998.
Maternal L‐carnitine supplementation improves glucose and lipid profiles in female offspring of dams exposed to cigarette smoke
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S Saad I Al‐Odat YL Chan KC McGrath CA Pollock BG Oliver H Chen 《Clinical and experimental pharmacology & physiology》2018,45(7):694-703
Sex differences in disease susceptibility due to maternal programming have been reported. We previously observed that maternal smoking induced renal disease and neurological changes are restricted to males, while both male and female offspring develop metabolic disorders. We have also found that maternal L‐carnitine supplementation during gestation and lactation can significantly improve glucose intolerance and hyperlipidaemia in male offspring. This study aimed to determine whether such beneficial effects can also occur in female offspring. Balb/c female mice were exposed to cigarette smoke (SE) 6 weeks prior to gestation, during gestation and lactation. A subgroup of the SE dams was given L‐carnitine (1.5 mmol/L in drinking water) during gestation and lactation. Female offspring were studied at 20 days (weaning) and 13 weeks (adulthood). Maternal smoking increased liver weight (%) and blood glucose levels at 20 days, as well as glucose intolerance and plasma triglycerides levels at adulthood (P < .05). The hepatic lipid metabolic marker adipose triglyceride lipase was downregulated in the SE offspring at 20 days (P < .05). At 13 weeks, the hepatic pro‐inflammatory markers IL‐1β and TNF‐α mRNA expression were upregulated, while the anti‐inflammatory marker IL‐10 mRNA expression was downregulated in the SE offspring (P < .05). Liver fibrosis was apparent at 20 days and 13 weeks. Maternal L‐carnitine supplementation either normalised or suppressed the detrimental effects induced by maternal smoke exposure (P < .05). We conclude that maternal L‐carnitine supplementation improves metabolic parameters in the female offspring of SE dams. 相似文献
999.
Matthew Parsons PhD MSc BSc RGN NZRN Paul Rouse PhD MCom BCom CA Laszlo Sajtos PhD MSc BSc Julie Harrison PhD MCom BCom CA Lisa Gestro BCom PGDip 《Health & social care in the community》2018,26(3):345-355
Worldwide increases in the numbers of older people alongside an accompanying international policy incentive to support ageing‐in‐place have focussed the importance of home‐care services as an alternative to institutionalisation. Despite this, funding models that facilitate a responsive, flexible approach are lacking. Casemix provides one solution, but the transition from the well‐established hospital system to community has been problematic. This research seeks to develop a Casemix funding solution for home‐care services through meaningful client profile groups and supporting pathways. Unique assessments from 3,135 older people were collected from two health board regions in 2012. Of these, 1,009 arose from older people with non‐complex needs using the interRAI‐Contact Assessment (CA) and 2,126 from the interRAI‐Home‐Care (HC) from older people with complex needs. Home‐care service hours were collected for 3 months following each assessment and the mean weekly hours were calculated. Data were analysed using a decision tree analysis, whereby mean hours of weekly home‐care was the dependent variable with responses from the assessment tools, the independent variables. A total of three main groups were developed from the interRAI‐CA, each one further classified into “stable” or “flexible.” The classification explained 16% of formal home‐care service hour variability. Analysis of the interRAI‐HC generated 33 clusters, organised through eight disability “sub” groups and five “lead” groups. The groupings explained 24% of formal home‐care services hour variance. Adopting a Casemix system within home‐care services can facilitate a more appropriate response to the changing needs of older people. 相似文献
1000.
Cognitive performance among the elderly and dietary fish intake: the Hordaland Health Study 总被引:1,自引:0,他引:1
Nurk E Drevon CA Refsum H Solvoll K Vollset SE Nygård O Nygaard HA Engedal K Tell GS Smith AD 《The American journal of clinical nutrition》2007,86(5):1470-1478
BACKGROUND: Increasing evidence suggests that cognitive impairment and dementia in older subjects might be influenced by a diet including seafood. OBJECTIVE: The objective was to examine the cross-sectional relation between intake of different amounts of various seafood (fish and fish products) and cognitive performance. DESIGN: The subjects (n = 2031 subjects; 55% women), aged 70-74 y, were recruited from the general population in Western Norway and underwent cognitive testing. A cognitive test battery included the Kendrick Object Learning Test, Trail Making Test (part A), modified versions of the Digit Symbol Test, Block Design, Mini-Mental State Examination, and Controlled Oral Word Association Test. Poor cognitive performance was defined as a score in the highest decile for the Trail Making Test and in the lowest decile for all other tests. RESULTS: Subjects whose mean daily intake of fish and fish products was >/=10 g/d (n = 1951) had significantly better mean test scores and a lower prevalence of poor cognitive performance than did those whose intake was <10 g/d (n = 80). The associations between total intake of seafood and cognition were strongly dose-dependent; the maximum effect was observed at an intake of approximately 75 g/d. Most cognitive functions were influenced by fish intake. The effect was more pronounced for nonprocessed lean fish and fatty fish. CONCLUSIONS: In the elderly, a diet high in fish and fish products is associated with better cognitive performance in a dose-dependent manner. 相似文献