全文获取类型
收费全文 | 665篇 |
免费 | 51篇 |
国内免费 | 4篇 |
出版年
2022年 | 5篇 |
2021年 | 9篇 |
2020年 | 2篇 |
2019年 | 12篇 |
2018年 | 7篇 |
2017年 | 10篇 |
2016年 | 12篇 |
2015年 | 25篇 |
2014年 | 39篇 |
2013年 | 40篇 |
2012年 | 48篇 |
2011年 | 45篇 |
2010年 | 23篇 |
2009年 | 34篇 |
2008年 | 33篇 |
2007年 | 33篇 |
2006年 | 41篇 |
2005年 | 44篇 |
2004年 | 42篇 |
2003年 | 54篇 |
2002年 | 44篇 |
2001年 | 10篇 |
2000年 | 9篇 |
1999年 | 7篇 |
1998年 | 7篇 |
1997年 | 5篇 |
1996年 | 8篇 |
1995年 | 5篇 |
1994年 | 9篇 |
1993年 | 2篇 |
1992年 | 4篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1989年 | 1篇 |
1988年 | 5篇 |
1987年 | 2篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 6篇 |
1982年 | 5篇 |
1981年 | 2篇 |
1980年 | 7篇 |
1979年 | 2篇 |
1978年 | 4篇 |
1977年 | 4篇 |
1974年 | 1篇 |
1972年 | 1篇 |
1969年 | 2篇 |
1967年 | 1篇 |
1966年 | 2篇 |
排序方式: 共有720条查询结果,搜索用时 15 毫秒
141.
Lotta Koskinen Jihane Romanos Katri Kaukinen Kirsi Mustalahti Ilma Korponay-Szabo Donatella Barisani Maria Teresa Bardella Fabiana Ziberna Serena Vatta György Széles Zsuzsa Pocsai Kati Karell Katri Haimila Róza Ádány Tarcisio Not Alessandro Ventura Markku Mäki Jukka Partanen Cisca Wijmenga Päivi Saavalainen 《Immunogenetics》2009,61(4):247-256
Human leukocyte antigen (HLA) genes, located on chromosome 6p21.3, have a crucial role in susceptibility to various autoimmune
and inflammatory diseases, such as celiac disease and type 1 diabetes. Certain HLA heterodimers, namely DQ2 (encoded by the
DQA1*05 and DQB1*02 alleles) and DQ8 (DQA1*03 and DQB1*0302), are necessary for the development of celiac disease. Traditional
genotyping of HLA genes is laborious, time-consuming, and expensive. A novel HLA-genotyping method, using six HLA-tagging
single-nucleotide polymorphisms (SNPs) and suitable for high-throughput approaches, was described recently. Our aim was to
validate this method in the Finnish, Hungarian, and Italian populations. The six previously reported HLA-tagging SNPs were
genotyped in patients with celiac disease and in healthy individuals from Finland, Hungary, and two distinct regions of Italy.
The potential of this method was evaluated in analyzing how well the tag SNP results correlate with the HLA genotypes previously
determined using traditional HLA-typing methods. Using the tagging SNP method, it is possible to determine the celiac disease
risk haplotypes accurately in Finnish, Hungarian, and Italian populations, with specificity and sensitivity ranging from 95%
to 100%. In addition, it predicts homozygosity and heterozygosity for a risk haplotype, allowing studies on genotypic risk
effects. The method is transferable between populations and therefore suited for large-scale research studies and screening
of celiac disease among high-risk individuals or at the population level.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Lotta Koskinen and Jihane Romanos are authors with equal contribution. 相似文献
142.
143.
Trine Well?v Boesgaard Anette Prior Gjesing Niels Grarup Jarno Rutanen Per-Anders Jansson Marta Letizia Hribal Giorgio Sesti Andreas Fritsche Norbert Stefan Harald Staiger Hans H?ring Ulf Smith Markku Laakso Oluf Pedersen Torben Hansen for the EUGENE Consortium 《PloS one》2009,4(9)
Backround
A meta-analysis combining results from three genome-wide association studies and followed by large-scale replication identified six novel type 2 diabetes loci. Subsequent studies of the effect of these variants on estimates of the beta-cell function and insulin sensitivity have been inconclusive. We examined these variants located in or near the JAZF1 (rs864745), THADA (rs7578597), TSPAN8 (rs7961581), ADAMTS9 (rs4607103), NOTCH2 (rs10923931) and the CDC123/CAMK1D (rs12779790) genes for associations with measures of pancreatic beta-cell function and insulin sensitivity.Methodology/Results
Oral and intravenous glucose stimulated insulin release (n = 849) and insulin sensitivity (n = 596) estimated from a hyperinsulinemic euglycemic clamp were measured in non-diabetic offspring of type 2 diabetic patients from five European populations. Assuming an additive genetic model the diabetes-associated major C-allele of rs4607103 near ADAMTS9 associated with reduced insulin-stimulated glucose uptake (p = 0.002) during a hyperinsulinemic euglycemic clamp. However, following intravenous and oral administration of glucose serum insulin release was increased in individuals with the C-allele (p = 0.003 and p = 0.01, respectively). A meta-analyse combining clamp and IVGTT data from a total of 905 non-diabetic individuals showed that the C-risk allele associated with decreased insulin sensitivity (p = 0.003) and increased insulin release (p = 0.002). The major T-allele of the intronic JAZF1 rs864745 conferring increased diabetes risk was associated with increased 2nd phase serum insulin release during an IVGTT (p = 0.03), and an increased fasting serum insulin level (p = 0.001). The remaining variants did not show any associations with insulin response, insulin sensitivity or any other measured quantitative traits.Conclusion
The present studies suggest that the diabetogenic impact of the C-allele of rs4607103 near ADAMTS9 may in part be mediated through decreased insulin sensitivity of peripheral tissues. 相似文献144.
Kalevi Salonen Matti Leppäranta Markku Viljanen Ramesh D. Gulati 《Aquatic Ecology》2009,43(3):607-608
145.
Petter D. Jenssen Tore Krogstad Adam M. Paruch Trond Mæhlum Kinga Adam Carlos A. Arias Arve Heistad Lena Jonsson Daniel Hellström Hans Brix Markku Yli-Halla Lasse Vråle Matti Valve 《Ecological Engineering》2010,36(12):1651-1659
Nine filter beds have been constructed in the Nordic countries, Denmark, Finland, Norway and Sweden. Filter beds consist of a septic tank followed by an aerobic pre-treatment biofilter and a subsequent saturated flow grass-covered filter. Thus, filter beds are similar to subsurface flow constructed wetlands with pre-treatment biofilters, but do not have wetland plants with roots submerged into the saturated filter. All saturated filters contain Filtralite®P, a light-weight expanded clay aggregate possessing high phosphorus sorption capacity. The filter bed systems showed stable and consistent performance during the testing period of 3 years. Removal of organic matter measured as biochemical oxygen demand (BOD) was >80%, total phosphorus (TP) >94% and total nitrogen (TN) ranged from 32 to 66%. Effluent concentrations of fecal indicator bacteria met the European bathing water quality criteria in all systems. One system was investigated for virus removal and somatic viruses were not detected in the effluent. The investigations revealed that the majority of the BOD and nitrogen removal occurred in the pre-treatment filters and the phosphorus and bacteria removal was more prominent in the saturated filters. The saturated filters could be built substantially smaller than the current design guidelines without sacrificing treatment performance. The used filter material met the Norwegian regulations for reuse in agriculture with respect to heavy metals, bacteria and parasites. When saturated with phosphorus, the light-weight aggregate, Filtralite®P used in the saturated bed is a suitable phosphorus fertilizer and additionally has a liming effect. 相似文献
146.
Mari Pekkanen-Mattila Markku Pelto-Huikko Ville Kujala Riitta Suuronen Heli Skottman Katriina Aalto-Setälä Erja Kerkelä 《Histochemistry and cell biology》2010,133(5):595-606
Human embryonic stem cell (hESC) differentiation in embryoid bodies (EBs) provides a valuable tool to study the interplay
of different germ layers and their influence on cell differentiation. The gene expression of the developing EBs has been shown
in many studies, but the protein expression and the spatial composition of different germ layers in human EBs have not been
systematically studied. The aim of the present work was to study the temporal and spatial organisation of germ layers based
on the expression of mesoderm (Brachyury T), endoderm (AFP) and ectoderm (SOX1) markers during the early stages of differentiation
in eight hESC lines. Tissue multi-array technology was applied to study the protein expression of a large number of EBs. According
to our results, EB formation and the organisation of germ layers occurred in a similar manner in all the lines. During 12 days
of differentiation, all the germ layer markers were present, but no obvious distinct trajectories were formed. However, older
EBs were highly organised in structure. Pluripotency marker OCT3/4 expression persisted unexpectedly long in the differentiating
EBs. Cavity formation was observed in the immunocytological sections, and caspase-3 expression was high, suggesting a role
of apoptosis in hESC differentiation and/or EB formation. The expression of Brachyury T was notably low in all the lines,
also those with the best cardiac differentiation capacity, while the expression of SOX1 was higher in some lines, suggesting
that the neural differentiation propensity may be detectable already in the early stages of EB differentiation. 相似文献
147.
Helena Gylling Maarit Hallikainen Jussi Pihlajam?ki Piia Simonen Johanna Kuusisto Markku Laakso Tatu A. Miettinen 《Journal of lipid research》2010,51(8):2422-2427
Cholesterol synthesis is upregulated and absorption downregulated in insulin resistance and in type 2 dia-betes. We investigated whether alterations in cholesterol metabolism are observed across the glucose tolerance status, from normoglycemia through impaired glucose tolerance to type 2 diabetes, in 781 randomly selected men 45 to 70 years of age from a population-based Metabolic Syndrome in Men Study. Cholesterol metabolism was assayed using surrogate serum markers, squalene, and noncholesterol sterols. The study population was classified into subgroups according to glucose tolerance as follows: normoglycemia, impaired fasting glucose, impaired glucose tolerance, and type 2 diabetes. LDL cholesterol did not differ between the groups. Cholesterol synthesis markers were lowest and absorption markers highest in normoglycemia. Sitosterol was lower in subjects with impaired fasting glucose compared with normoglycemic subjects (113 ± 7 vs. 136 ± 3 102 μmol/mmol of cholesterol, P < 0.05). LDL cholesterol was not associated with lathosterol/sitosterol ratio, a marker of cholesterol metabolism. Peripheral insulin sensitivity evaluated by the Matsuda index was associated with the lathosterol/sitosterol ratio in the entire population (r = −0.457, P < 0.001) and with that of lathosterol/cholestanol independently of obesity. In conclusion, cholesterol metabolism was altered already from subjects with impaired fasting glucose. Upregulated cholesterol synthesis was associated with peripheral insulin resistance independent of obesity. 相似文献
148.
Markku Larjavaara 《Journal of theoretical biology》2010,265(1):63-124
Wind routinely topples trees during storms, and the likelihood that a tree is toppled depends critically on its allometry. Yet none of the existing theories to explain tree allometry consider wind drag on tree canopies. Since leaf area index in crowded, self-thinning stands is independent of stand density, the drag force per unit land can also be assumed to be independent of stand density, with only canopy height influencing the total toppling moment. Tree stem dimensions and the self-thinning biomass can then be computed by further assuming that the risk of toppling over and stem maintenance per unit land area are independent of stand density, and that stem maintenance cost is a linear function of stem surface area and sapwood volume. These assumptions provide a novel way to understand tree allometry and lead to a self-thinning line relating tree biomass and stand density with a power between −3/2 and −2/3 depending on the ratio of maintenance of sapwood and stem surface. 相似文献
149.
Marshall Nathaniel S. Grunstein Ron R. Peltonen Markku Stenlof Kaj Hedner Jan Sjostrom Lars V. 《Sleep and biological rhythms》2010,8(1):63-71
Sleep and Biological Rhythms - Sleep duration has been linked to obesity and/or weight gain in a number of cross-sectional and longitudinal observational studies. The Swedish Obese Subjects Study... 相似文献
150.
Anne Kultti Riikka K?rn? Kirsi Rilla Pertti Nurminen Elina Koli Katri M. Makkonen Jutong Si Markku I. Tammi Raija H. Tammi 《The Journal of biological chemistry》2010,285(30):22901-22910
Hyaluronan synthases (HAS1–3) are integral plasma membrane proteins that synthesize hyaluronan, a cell surface and extracellular matrix polysaccharide necessary for many biological processes. It has been shown that HAS is partly localized in cholesterol-rich lipid rafts of MCF-7 cells, and cholesterol depletion with methyl-β-cyclodextrin (MβCD) suppresses hyaluronan secretion in smooth muscle cells. However, the mechanism by which cholesterol depletion inhibits hyaluronan production has remained unknown. We found that cholesterol depletion from MCF-7 cells by MβCD inhibits synthesis but does not decrease the molecular mass of hyaluronan, suggesting no major influence on HAS stability in the membrane. The inhibition of hyaluronan synthesis was not due to the availability of HAS substrates UDP-GlcUA and UDP-GlcNAc. Instead, MβCD specifically down-regulated the expression of HAS2 but not HAS1 or HAS3. Screening of signaling proteins after MβCD treatment revealed that phosphorylation of Akt and its downstream target p70S6 kinase, both members of phosphoinositide 3-kinase-Akt pathway, were inhibited. Inhibitors of this pathway suppressed hyaluronan synthesis and HAS2 expression in MCF-7 cells, suggesting that the reduced hyaluronan synthesis by MβCD is due to down-regulation of HAS2, mediated by the phosphoinositide 3-kinase-Akt-mTOR-p70S6K pathway. 相似文献