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排序方式: 共有248条查询结果,搜索用时 31 毫秒
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Various types of thalassemia or hereditary persistence of fetal hemoglobin (HPFH) are caused by deletions at the human beta-globin gene cluster. Many of these molecular lesions show a clear clustering as far as size and location of their breakpoints are concerned. This might indicate common recombination mechanisms responsible for the generation of these deletions. The Belgian G gamma+(A gamma delta beta)zero-thalassemia results from a large deletion spanning the beta-globin gene cluster 3' of the A gamma gene. The extent of this deletion, analyzed by field-inversion gel electrophoresis, is approximately 50 kb and is very similar to that of the Indian HPFH (G gamma A gamma HPFH III) previously characterized by P. S. Henthorn et al. (1986). Proc. Natl. Acad. Sci. USA 83: 5194-5198. Isolation of the deletion junction of the Belgian G gamma+(A gamma delta beta)zero-thalassemia by means of inverse polymerase chain reaction confirmed a very close relationship between these two independent deletions. The 3' breakpoint of the Belgian deletion is located at the midpoint of a 160-bp palindrome, only four nucleotides 5' from the correspondent endpoint of the Indian HPFH. 相似文献
3.
Elferra M. Swart Naima C. Starkloff Sanne Ypenburg Jacintha Ellers Nico M. van Straalen Joris M. Koene 《Invertebrate Biology》2020,139(1)
Sexual conflicts often arise between mating partners because each sex tries to maximize its own reproductive success. One major male strategy to influence a partner's resource allocation is the transfer of accessory gland proteins. This has been shown to occur in simultaneous hermaphrodites as well as in organisms with separate sexes. Although accessory gland proteins affect the investment of resources in both male and female function, we here specifically focus on female investment. In the great pond snail, Lymnaea stagnalis, previous studies found that the accessory gland protein ovipostatin reduced female fecundity by suppressing egg laying in the partner in the short term (days). To investigate whether this reduction in egg laying is a commonly found effect of mating in freshwater snails, we compared egg output for evidence of suppression in isolated and paired snails of eight pulmonate species. Furthermore, we determined whether the suppression of egg laying caused a shift in resource allocation to the eggs. We found that in five of the eight species egg laying was suppressed, with fewer and lighter egg masses being laid when they had access to a mating partner. In mated pairs of L. stagnalis and Biomphalaria alexandrina, allocation of resources to the eggs was altered in opposite ways: individuals of L. stagnalis laid fewer but larger and heavier eggs; individuals of B. alexandrina laid smaller and lighter eggs, with no change in egg numbers. Such changes in the female function are most likely the result of combined effects of receiving accessory gland proteins, and the cost of mating in both male and female roles. Thus, effects of the maternal environment, including the receipt of accessory gland proteins, on offspring investment are not restricted to species with separate sexes. 相似文献
4.
S?s Neergaard-Petersen Ramzi Ajjan Anne-Mette Hvas Katharina Hess Sanne B?jet Larsen Steen Dalby Kristensen Erik Lerkevang Grove 《PloS one》2013,8(8)
Background
Aspirin is a cornerstone in prevention of cardiovascular events and modulates both platelet aggregation and fibrin clot formation. Some patients experience cardiovascular events whilst on aspirin, often termed aspirin treatment failure (ATF). This study evaluated both platelet aggregation and fibrin clot structure in patients with ATF.Methods
We included 177 stable coronary artery disease patients on aspirin monotherapy. Among these, 116 (66%) had ATF defined as myocardial infarction (MI) whilst on aspirin. Platelet aggregation was assessed by Multiplate® aggregometry and VerifyNow®, whereas turbidimetric assays and scanning electron microscopy were employed to study fibrin clot characteristics.Results
Enhanced platelet aggregation was observed in patients with ATF compared with non-MI patients following stimulation with arachidonic acid 1.0 mM (median 161 (IQR 95; 222) vs. 97 (60; 1776) AU*min, p = 0.005) and collagen 1.0 µg/mL (293 (198; 427) vs. 220 (165; 370) AU*min, p = 0.03). Similarly, clot maximum absorbance, a measure of fibrin network density, was increased in patients with ATF (0.48 (0.41; 0.52) vs. 0.42 (0.38; 0.50), p = 0.02), and this was associated with thinner fibres (mean ± SD: 119.7±27.5 vs. 127.8±31.1 nm, p = 0.003) and prolonged lysis time (552 (498; 756) vs. 519 (468; 633) seconds; p = 0.02). Patients with ATF also had increased levels of C-reactive protein (CRP) (1.34 (0.48; 2.94) and 0.88 (0.32; 1.77) mg/L, p = 0.01) compared with the non-MI group. Clot maximum absorbance correlated with platelet aggregation (r = 0.31–0.35, p-values<0.001) and CRP levels (r = 0.60, p<0.001).Conclusions
Patients with aspirin treatment failure showed increased platelet aggregation and altered clot structure with impaired fibrinolysis compared with stable CAD patients without previous MI. These findings suggest that an increased risk of aspirin treatment failure may be identified by measuring both platelet function and fibrin clot structure. 相似文献5.
Anna H. van’t Hoog Frank Cobelens Anna Vassall Sanne van Kampen Susan E. Dorman David Alland Jerrold Ellner 《PloS one》2013,8(12)
Background
High costs are a limitation to scaling up the Xpert MTB/RIF assay (Xpert) for the diagnosis of tuberculosis in resource-constrained settings. A triaging strategy in which a sensitive but not necessarily highly specific rapid test is used to select patients for Xpert may result in a more affordable diagnostic algorithm. To inform the selection and development of particular diagnostics as a triage test we explored combinations of sensitivity, specificity and cost at which a hypothetical triage test will improve affordability of the Xpert assay.Methods
In a decision analytical model parameterized for Uganda, India and South Africa, we compared a diagnostic algorithm in which a cohort of patients with presumptive TB received Xpert to a triage algorithm whereby only those with a positive triage test were tested by Xpert.Findings
A triage test with sensitivity equal to Xpert, 75% specificity, and costs of US$5 per patient tested reduced total diagnostic costs by 42% in the Uganda setting, and by 34% and 39% respectively in the India and South Africa settings. When exploring triage algorithms with lower sensitivity, the use of an example triage test with 95% sensitivity relative to Xpert, 75% specificity and test costs $5 resulted in similar cost reduction, and was cost-effective by the WHO willingness-to-pay threshold compared to Xpert for all in Uganda, but not in India and South Africa. The gain in affordability of the examined triage algorithms increased with decreasing prevalence of tuberculosis among the cohort.Conclusions
A triage test strategy could potentially improve the affordability of Xpert for TB diagnosis, particularly in low-income countries and with enhanced case-finding. Tests and markers with lower accuracy than desired of a diagnostic test may fall within the ranges of sensitivity, specificity and cost required for triage tests and be developed as such. 相似文献6.
Sanne R. Martens-de Kemp Arjen Brink Marijke Stigter-van Walsum J. Mirjam A. Damen François Rustenburg Thijs Wu Wessel N. van Wieringen Gerrit Jan Schuurhuis Boudewijn J.M. Braakhuis Monique Slijper Ruud H. Brakenhoff 《Stem cell research》2013,10(3):477-488
Patients with advanced head and neck squamous cell carcinomas (HNSCCs) are often treated with concomitant chemotherapy and radiotherapy, but only 50% is cured. A possible explanation for treatment failure is therapy resistance of the cancer stem cells (CSCs). The application of compounds specifically targeting these CSCs, in addition to routinely used therapeutics, would likely improve clinical outcome. We demonstrate that the previously described monoclonal antibody K984 recognizes the CD98 cell surface protein, which is specifically expressed by cells forming the squamous basal cell layer, the region where the squamous stem cells reside. Moreover, CD98 is highly resistant to the proteolytic enzymes required for CSC enrichment procedures. We show that CD98high cells, in contrast to CD98low cells, are able to generate tumors in immunodeficient mice, indicating that CD98high cells have stem cell characteristics. Furthermore, the CD98high subpopulation expresses high levels of cell cycle control and DNA repair genes, while the CD98low fraction shows expression patterns that represent the more differentiated cells forming the bulk of the tumor. CD98 is a promising CSC enrichment marker in HNSCC. Our data support the CSC concept in head and neck cancer and the potential relevance of these cells for treatment outcome. 相似文献
7.
Sanne P. M. Verhoef Stefan G. J. A. Camps Freek G. Bouwman Edwin C. M. Mariman Klaas R. Westerterp 《PloS one》2013,8(3)
Background
Metabolic processes in adipose tissue are dysregulated in obese subjects and, in response to weight loss, either normalize or change in favor of weight regain.Objective
To determine changes in adipocyte glucose and fatty acid metabolism in relation to changes in adipocyte size during weight loss and maintenance.Methods
Twenty-eight healthy subjects (12 males), age 20–50 y, and BMI 28–35 kg/m2, followed a very low energy diet for 2 months, followed by a 10-month period of weight maintenance. Body weight, body composition (deuterium dilution and BodPod), protein levels (Western blot) and adipocyte size were assessed prior to and after weight loss and after the 10-month follow-up.Results
A 10% weight loss resulted in a 16% decrease in adipocyte size. A marker for glycolysis decreased (AldoC) during weight loss in association with adipocyte shrinking, and remained decreased during follow-up in association with weight maintenance. A marker for fatty acid transport increased (FABP4) during weight loss and remained increased during follow-up. Markers for mitochondrial beta-oxidation (HADHsc) and lipolysis (ATGL) were only increased after the 10-month follow-up. During weight loss HADHsc and ATGL were coordinately regulated, which became weaker during follow-up due to adipocyte size-related changes in HADHsc expression. AldoC was the major denominator of adipocyte size and body weight, whereas changes in ATGL during weight loss contributed to body weight during follow-up. Upregulation of ATGL and HADHsc occured in the absence of a negative energy balance and was triggered by adipocyte shrinkage or indicated preadipocyte differentiation.Conclusion
Markers for adipocyte glucose and fatty acid metabolism are changed in response to weight loss in line with normalization from a dysregulated obese status to an improved metabolic status.Trial Registration
ClinicalTrials.gov NCT01015508相似文献8.
Ole J Hamming Ewa Terczyńska‐Dyla Gabrielle Vieyres Ronald Dijkman Sanne E Jørgensen Hashaam Akhtar Piotr Siupka Thomas Pietschmann Volker Thiel Rune Hartmann 《The EMBO journal》2013,32(23):3055-3065
The IFNL4 gene is a recently discovered type III interferon, which in a significant fraction of the human population harbours a frameshift mutation abolishing the IFNλ4 ORF. The expression of IFNλ4 is correlated with both poor spontaneous clearance of hepatitis C virus (HCV) and poor response to treatment with type I interferon. Here, we show that the IFNL4 gene encodes an active type III interferon, named IFNλ4, which signals through the IFNλR1 and IL‐10R2 receptor chains. Recombinant IFNλ4 is antiviral against both HCV and coronaviruses at levels comparable to IFNλ3. However, the secretion of IFNλ4 is impaired compared to that of IFNλ3, and this impairment is not due to a weak signal peptide, which was previously believed. We found that IFNλ4 gets N‐linked glycosylated and that this glycosylation is required for secretion. Nevertheless, this glycosylation is not required for activity. Together, these findings result in the paradox that IFNλ4 is strongly antiviral but a disadvantage during HCV infection. 相似文献
9.
The gap between the number of known protein sequences and structures continues to widen, particularly as a result of sequencing projects for entire genomes. Recently there have been many attempts to generate structural assignments to all genes on sets of completed genomes using fold-recognition methods. We developed a method that detects false positives made by these genome-wide structural assignment experiments by identifying isolated occurrences. The method was tested using two sets of assignments, generated by SUPERFAMILY and PSI-BLAST, on 150 completed genomes. A phylogeny of these genomes was built and a parsimony algorithm was used to identify isolated occurrences by detecting occurrences that cause a gain at leaf level. Isolated occurrences tend to have high e-values, and in both sets of assignments, a sudden increase in isolated occurrences is observed for e-values >10−8 for SUPERFAMILY and >10−4 for PSI-BLAST. Conditions to predict false positives are based on these results. Independent tests confirm that the predicted false positives are indeed more likely to be incorrectly assigned. Evaluation of the predicted false positives also showed that the accuracy of profile-based fold-recognition methods might depend on secondary structure content and sequence length. We show that false positives generated by fold-recognition methods can be identified by considering structural occurrence patterns on completed genomes; occurrences that are isolated within the phylogeny tend to be less reliable. The method provides a new independent way to examine the quality of fold assignments and may be used to improve the output of any genome-wide fold assignment method. 相似文献
10.