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排序方式: 共有171条查询结果,搜索用时 15 毫秒
1.
Arto Mannermaa Hellevi Peltoketo Robert Winqvist Bruce A. J. Ponder Heikki Kiviniemi Douglas F. Easton Matti Poutanen Veli Isomaa Reijo Vihko 《Human genetics》1994,93(3):319-324
17-Hydroxysteroid dehydrogenase (17HSD) is one of the key enzymes in estrogen metabolism, catalyzing the reversible reaction between estradiol and the less active estrogen, estrone. The gene encoding this enzyme, EDH17B2, has been mapped to chromosome 17, region q12–q21, in the vicinity of BRCA1, an as yet unidentified gene that appears to be involved in familial breast cancer and in familial ovarian cancer. The possibility that EDH17B2 gene is the same as BRCA1 was tested by screening for mutations in the coding regions of EDH17B2, using a polymerase chain reaction/single-strand conformation polymorphism method. An AG transition creating a new BstUI site at exon 6 was the only frequent sequence alteration found in the coding region of the gene. This mutation also led to an amino acid substitution of serine to glycine at position 312 (312S312G) in the 17HSD protein. Since the nucleotide change was detected both in specimens from patients with familial or sporadic cancer and in control samples, and at similar rates, this mutation appears to be of a polymorphic nature. In addition, a rare polymorphism located at intron 5 was detected. This CT substitution creates a BbvI site and is not thought to have any effect on 17HSD activity. The results indicate that there are no major alterations in the coding areas of EDH17B2 and thus studies testing the hypothesis that EDH17B2 may be the same as BRCA1 should be extended to the promoter and regulatory elements of EDH17B2. 相似文献
2.
Arto Y. Strandberg Fabian J. Hoti Timo E. Strandberg Solomon Christopher Jari Haukka Pasi Korhonen 《PloS one》2016,11(3)
Background
Insulin therapy in type 2 diabetes may increase mortality and cancer incidence, but the impact of different types of basal insulins on these endpoints is unclear. Compared to the traditional NPH insulin, the newer, longer-acting insulin analogues detemir and glargine have shown benefits in randomized controlled trials. Whether these advantages translate into lower mortality among users in real life is unknown.Objective
To estimate the differences in all-cause and cause-specific mortality rates between new users of basal insulins in a population-based study in Finland.Methods
23 751 individuals aged ≥40 with type 2 diabetes, who initiated basal insulin therapy in 2006–2009 were identified from national registers, with comprehensive data for mortality, causes of death, and background variables. Propensity score matching was performed on characteristics. Follow-up time was up to 4 years (median 1.7 years).Results
2078 deaths incurred. With NPH as reference, the adjusted HRs for all-cause mortality were 0.39 (95% CI, 0.30–0.50) for detemir, and 0.55 (95% CI, 0.44–0.69) for glargine. As compared to glargine, the HR was 0.71 (95% CI, 0.54–0.93) among detemir users. Compared to NPH, the mortality risk for both cardiovascular causes as well as cancer were also significantly lower for glargine, and especially for detemir in adjusted analysis. Furthermore, the results were robust in various sensitivity analyses.Conclusion
In real clinical practice, mortality was substantially higher among users of NPH insulin as compared to insulins detemir or glargine. Considering the large number of patients who require insulin therapy, this difference in risk may have major clinical and public health implications. Due to limitations of the observational study design, further investigation using an interventional study design is warranted. 相似文献3.
Robert?M. Glaeser Bong-Gyoon Han Roseann Csencsits Alison Killilea Arto Pulk Jamie?H.D. Cate 《Biophysical journal》2016,110(4):749-755
Poor consistency of the ice thickness from one area of a cryo-electron microscope (cryo-EM) specimen grid to another, from one grid to the next, and from one type of specimen to another, motivates a reconsideration of how to best prepare suitably thin specimens. Here we first review the three related topics of wetting, thinning, and stability against dewetting of aqueous films spread over a hydrophilic substrate. We then suggest that the importance of there being a surfactant monolayer at the air-water interface of thin, cryo-EM specimens has been largely underappreciated. In fact, a surfactant layer (of uncontrolled composition and surface pressure) can hardly be avoided during standard cryo-EM specimen preparation. We thus suggest that better control over the composition and properties of the surfactant layer may result in more reliable production of cryo-EM specimens with the desired thickness. 相似文献
4.
Quaternary structure built from subunits combining NMR and small-angle x-ray scattering data 总被引:5,自引:0,他引:5 下载免费PDF全文
Mattinen ML Pääkkönen K Ikonen T Craven J Drakenberg T Serimaa R Waltho J Annila A 《Biophysical journal》2002,83(2):1177-1183
A new principle in constructing molecular complexes from the known high-resolution domain structures joining data from NMR and small-angle x-ray scattering (SAXS) measurements is described. Structure of calmodulin in complex with trifluoperazine was built from N- and C-terminal domains oriented based on residual dipolar couplings measured by NMR in a dilute liquid crystal, and the overall shape of the complex was derived from SAXS data. The residual dipolar coupling data serves to reduce angular degrees of freedom, and the small-angle scattering data serves to confine the translational degrees of freedom. The complex built by this method was found to be consistent with the known crystal structure. The study demonstrates how approximate tertiary structures of modular proteins or quaternary structures composed of subunits can be assembled from high-resolution structures of domains or subunits using mutually complementary NMR and SAXS data. 相似文献
5.
6.
Arto Laukkanen Arto Juhani Pesola Risto Heikkinen Arja Kaarina S??kslahti Taija Finni 《PloS one》2015,10(10)
Little is known of how to involve families in physical activity (PA) interventions for children. In this cluster randomized controlled trial, we recruited families with four- to seven-year-old children to participate in a year-long study where parents in the intervention group families (n = 46) received tailored counseling to increase children’s PA. Structured PA was not served. Control group families (n = 45) did not receive any counseling. PA in all children (n = 91; mean age 6.16 ± 1.13 years at the baseline) was measured by accelerometers at the baseline and after three, six, nine and 12 months. Motor competence (MC) (n = 89) was measured at the baseline and after six and 12 months by a KTK (KörperkoordinationsTest für Kinder) and throwing and catching a ball (TCB) protocols. The effect of parental counseling on study outcomes was analyzed by a linear mixed-effects model fit by REML and by a Mann-Whitney U test in the case of the TCB. As season was hypothesized to affect counseling effect, an interaction of season on the study outcomes was examined. The results show significant decrease of MVPA in the intervention group when compared to the control group (p < .05). The TCB showed a nearly significant improvement at six months in the intervention group compared to the controls (p = .051), but not at 12 months. The intervention group had a steadier development of the KTK when the interaction of season was taken into account. In conclusion, more knowledge of family constructs associating with the effectiveness of counseling is needed for understanding how to enhance PA in children by parents. However, a hypothesis may be put forward that family-based counseling during an inactive season rather than an active season may provide a more lasting effect on the development of KTK in children.
Trial Registration
Controlled-Trials.com ISRCTN28668090 相似文献7.
Arto Pulk Aivar Liiv Lauri Peil Ülo Maiväli Knud Nierhaus Jaanus Remme 《Molecular microbiology》2010,75(4):801-814
Ribosomal functions are vital for all organisms. Bacterial ribosomes are stable 2.4 MDa particles composed of three RNAs and over 50 different proteins. Accumulating damage to ribosomal RNA or proteins can disturb ribosome functioning. Organisms could benefit from degrading or possibly repairing inactive or partially active ribosomes. Reactivation of chemically damaged ribosomes by a process of protein replacement was studied in vitro. Ribosomes were inactivated by chemical modification of Cys residues. Incubation of modified ribosomes with total ribosomal proteins led to reactivation of translational activity. Intriguingly, ribosomal proteins extracted by LiCl are equally active in the restoration of ribosome function. Incubation of 70S ribosomes with isotopically labelled r‐proteins followed by separation of ribosomes was used to identify exchangeable proteins. A similar set of proteins was found to be exchanged in vivo under stress conditions in the stationary phase. We propose that repair of damaged ribosomes might be an important mechanism for maintaining protein synthesis activity following chemical damage. 相似文献
8.
Mice deficient in involucrin, envoplakin, and periplakin have a defective epidermal barrier 总被引:2,自引:0,他引:2 下载免费PDF全文
Sevilla LM Nachat R Groot KR Klement JF Uitto J Djian P Määttä A Watt FM 《The Journal of cell biology》2007,179(7):1599-1612
The cornified envelope is assembled from transglutaminase cross-linked proteins and lipids in the outermost epidermal layers and is essential for skin barrier function. Involucrin, envoplakin, and periplakin form the protein scaffold on which the envelope assembles. To examine their combined function, we generated mice deficient in all three genes. The triple knockouts have delayed embryonic barrier formation and postnatal hyperkeratosis (abnormal accumulation of cornified cells) resulting from impaired desquamation. Cornified envelopes form but are ultrastructurally abnormal, with reduced lipid content and decreased mechanical integrity. Expression of proteases is reduced and the protease inhibitor, serpina1b, is highly upregulated, resulting in defective filaggrin processing and delayed degradation of desmoglein 1 and corneodesmosin. There is infiltration of CD4+ T cells and a reduction in resident γδ+ T cells, reminiscent of atopic dermatitis. Thus, combined loss of the cornified envelope proteins not only impairs the epidermal barrier, but also changes the composition of T cell subpopulations in the skin. 相似文献
9.
Paasonen L Romberg B Storm G Yliperttula M Urtti A Hennink WE 《Bioconjugate chemistry》2007,18(6):2131-2136
We prepared thermosensitive poly( N-(2-hydroxypropyl)methacrylamide mono/dilactate) (pHPMA mono/dilactate) polymer and studied temperature-triggered contents release from polymer-coated liposomes. HPMA mono/dilactate polymer was synthesized with a cholesterol anchor suitable for incorporation in the liposomal bilayers and with a cloud point (CP) temperature of the polymer slightly above normal body temperature (42 degrees C). Dynamic light scattering (DLS) measurements showed that whereas the size of noncoated liposomes remained stable upon raising the temperature from 25 to 46 degrees C, polymer-coated liposomes aggregated around 43 degrees C. Also, noncoated liposomes loaded with calcein showed hardly any leakage of the fluorescent marker when heated to 46 degrees C. However, polymer-coated liposomes showed a high degree of temperature-triggered calcein release above the CP of the polymer. Likely, liposome aggregation and bilayer destabilization are triggered because of the precipitation of the thermosensitive polymer above its CP onto the liposomal bilayers, followed by permeabilization of the liposomal membrane. This study demonstrates that liposomes surface-modified with HPMA mono/dilactate copolymer are attractive systems for achieving temperature-triggered contents release. 相似文献
10.
Tiia Pedusaar Ilkka Sammalkorpi Arto Hautala Jaana Salujõe Ain Järvalt Margus Pihlak 《Hydrobiologia》2010,649(1):95-106
Lake ülemiste, the drinking water reservoir of Estonia’s capital city Tallinn, was biomanipulated by manual removal of cyprinids
in 2004–2006 and its impact on water quality in the vegetation period was studied. A total biomass of 156 tonnes corresponding
to 160 kg ha−1 of fish, predominantly cyprinids, were removed. A decline in the unit catches of fishing was observed. The removed fish biomass
versus phosphorus concentration of the lake was considered sufficient to reduce the impact of cyprinids on water quality.
The phosphorus removed within fish biomass corresponded to 38 μg l−1 and 21% of the external phosphorus load of the fishing period. The mean total phosphorus concentration dropped from >50 to
≤36 μg l−1. However, the densities of planktivorous young-of-the-year percids remained high and the role of zooplankton grazing in improving
water quality was found non-significant or transient. The cladocerans biomass decreased and the small-sized Daphnia cucullata remained almost the only daphnid in Lake ülemiste during and after the manipulation. Predomination of filamentous cyanobacteria
was replaced by a more diverse phytoplankton composition and co-domination of micro- and pico-sized colonial cyanobacteria
during summer. Mean phytoplankton biomass decreased from 15 to 6 mg l−1 primarily as a result of decreased in-lake TP availability. The Secchi disc transparency increased only in May 2005–2007.
The effects of coincidental events, a decline of external loading of phosphorus and a simultaneous flushing induced by heavy
rainfall, on lake water quality are discussed with some implications to the future management of the reservoir. 相似文献