全文获取类型
收费全文 | 555篇 |
免费 | 43篇 |
专业分类
598篇 |
出版年
2023年 | 1篇 |
2022年 | 12篇 |
2021年 | 24篇 |
2020年 | 11篇 |
2019年 | 12篇 |
2018年 | 16篇 |
2017年 | 15篇 |
2016年 | 20篇 |
2015年 | 32篇 |
2014年 | 31篇 |
2013年 | 37篇 |
2012年 | 52篇 |
2011年 | 58篇 |
2010年 | 23篇 |
2009年 | 24篇 |
2008年 | 37篇 |
2007年 | 42篇 |
2006年 | 30篇 |
2005年 | 23篇 |
2004年 | 26篇 |
2003年 | 27篇 |
2002年 | 25篇 |
2001年 | 1篇 |
2000年 | 2篇 |
1999年 | 3篇 |
1997年 | 4篇 |
1996年 | 1篇 |
1995年 | 3篇 |
1994年 | 2篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1979年 | 1篇 |
1970年 | 1篇 |
排序方式: 共有598条查询结果,搜索用时 15 毫秒
71.
Emilia Rabia Vronique Garambois Julie Hubert Marine Bruciamacchie Nelly Pirot Hlne Delpech Morgane Broyon Charles Theillet Pierre-Emmanuel Colombo Nadia Vie Diego Tosi Celine Gongora Lakhdar Khellaf Marta Jarlier Nina Radosevic-Robin Thierry Chards Andr Plegrin Christel Larbouret 《MABS-AUSTIN》2021,13(1)
72.
Alice Matone Marie-Pier Scott-Boyer Jerome Carayol Parastoo Fazelzadeh Gregory Lefebvre Armand Valsesia Celine Charon Jacques Vervoort Arne Astrup Wim H. M. Saris Melissa Morine J?rg Hager 《PloS one》2016,11(3)
Background and Scope
Weight loss success is dependent on the ability to refrain from regaining the lost weight in time. This feature was shown to be largely variable among individuals, and these differences, with their underlying molecular processes, are diverse and not completely elucidated. Altered plasma metabolites concentration could partly explain weight loss maintenance mechanisms. In the present work, a systems biology approach has been applied to investigate the potential mechanisms involved in weight loss maintenance within the Diogenes weight-loss intervention study.Methods and Results
A genome wide association study identified SNPs associated with plasma glycine levels within the CPS1 (Carbamoyl-Phosphate Synthase 1) gene (rs10206976, p-value = 4.709e-11 and rs12613336, p-value = 1.368e-08). Furthermore, gene expression in the adipose tissue showed that CPS1 expression levels were associated with successful weight maintenance and with several SNPs within CPS1 (cis-eQTL). In order to contextualize these results, a gene-metabolite interaction network of CPS1 and glycine has been built and analyzed, showing functional enrichment in genes involved in lipid metabolism and one carbon pool by folate pathways.Conclusions
CPS1 is the rate-limiting enzyme for the urea cycle, catalyzing carbamoyl phosphate from ammonia and bicarbonate in the mitochondria. Glycine and CPS1 are connected through the one-carbon pool by the folate pathway and the urea cycle. Furthermore, glycine could be linked to metabolic health and insulin sensitivity through the betaine osmolyte. These considerations, and the results from the present study, highlight a possible role of CPS1 and related pathways in weight loss maintenance, suggesting that it might be partly genetically determined in humans. 相似文献73.
Louh GN Lannang AM Mbazoa CD Tangmouo JG Komguem J Castilho P Ngninzeko FN Qamar N Lontsi D Choudhary MI Sondengam BL 《Phytochemistry》2008,69(4):1013-1017
Three xanthones, polyanxanthone A (1), B (2) and C (3) have been isolated from the methanol extract of the wood trunk of Garcinia polyantha, along with five known xanthones: 1,3,5-trihydroxyxanthone (4); 1,5-dihydroxyxanthone (5); 1,3,6,7-tetrahydroxyxanthone (6); 1,6-dihydroxy-5-methoxyxanthone (7) and 1,3,5,6-tetrahydroxyxanthone (8). Their structures were determined by means of 1D- and 2D-NMR techniques. Some of the above compounds were screened for their anticholinesterase activity on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. 相似文献
74.
Identification of a new segment involved in cagA 3' region variation of Helicobacter pylori 总被引:2,自引:0,他引:2
Dong Q O'Sullivan M Hall W Herra C Kean C O'Morain C Buckley M 《FEMS immunology and medical microbiology》2002,33(1):51-55
The cagA 3' region shows marked variation among Helicobacter pylori strains. Two segments of 102 bp and 57 bp are reportedly responsible for this variation. We analysed the cagA 3' region in 70 H. pylori strains using polymerase chain reaction and sequencing. We found that another segment, namely beta segment, was also involved in the variation of this region. The beta segment was 105 bp long and located between the aforementioned two segments. Six genotypes were identified based on the structure of the cagA 3' region. No relationship was found between these genotypes and the clinical outcomes or vacA genotypes. The numbers of tyrosine phosphorylation sites within the cagA 3' region varied among strains, but this was not related to the cagA genotypes. Our data suggest that the cagA 3' region is significantly variable. It appears that the variation of the cagA 3' region might contribute to the modification of virulence. 相似文献
75.
76.
Guillaume Emaresi Anne‐Lyse Ducrest Pierre Bize Hannes Richter Celine Simon Alexandre Roulin 《Molecular ecology》2013,22(19):4915-4930
The adaptive function of melanin‐based coloration is a long‐standing debate. A recent genetic model suggested that pleiotropy could account for covariations between pigmentation, behaviour, morphology, physiology and life history traits. We explored whether the expression levels of genes belonging to the melanocortin system (MC1R, POMC, PC1/3, PC2 and the antagonist ASIP), which have many pleiotropic effects, are associated with melanogenesis (through variation in the expression of the genes MITF, SLC7A11, TYR, TYRP1) and in turn melanin‐based coloration. We considered the tawny owl (Strix aluco) because individuals vary continuously from light to dark reddish, and thus, colour variation is likely to stem from differences in the levels of gene expression. We measured gene expression in feather bases collected in nestlings at the time of melanin production. As expected, the melanocortin system was associated with the expression of melanogenic genes and pigmentation. Offspring of darker reddish fathers expressed PC1/3 to lower levels but tended to express PC2 to higher levels. The convertase enzyme PC1/3 cleaves the POMC prohormone to obtain ACTH, while the convertase enzyme PC2 cleaves ACTH to produce α‐melanin‐stimulating hormone (α‐MSH). ACTH regulates glucocorticoids, hormones that modulate stress responses, while α‐MSH induces eumelanogenesis. We therefore conclude that the melanocortin system, through the convertase enzymes PC1/3 and PC2, may account for part of the interindividual variation in melanin‐based coloration in nestling tawny owls. Pleiotropy may thus account for the covariation between phenotypic traits involved in social interactions (here pigmentation) and life history, morphology, behaviour and physiology. 相似文献
77.
Repeatability and correlation of physiological traits: Do ectotherms have a “thermal type”? 下载免费PDF全文
Across a range of taxa, individuals within a species differ in suites of correlated traits. These trait complexes, known as syndromes, can have dramatic evolutionary consequences as they do not evolve independently but rather as a unit. Current research focuses primarily on syndromes relating to aspects of behavior and life history. What is less clear is whether physiological traits also form a syndrome. We measured 10 thermal traits in the delicate skink, Lampropholis delicata, to test this idea. Repeatability was calculated and their across‐context correlations evaluated. Our results were in alignment with our predictions in that individual thermal traits varied consistently and were structured into a physiological syndrome, which we are referring to as the thermal behavior syndrome (TBS). Within this syndrome, lizards exhibited a “thermal type” with each being ranked along a cold–hot continuum. Hot types had faster sprint speeds and higher preferred body temperatures, whereas the opposite was true for cold types. We conclude that physiological traits may evolve as a single unit driven by the need to maintain optimal temperatures that enable fitness‐related behaviors to be maximized. 相似文献
78.
de Andrade M Atkinson EJ Bamlet WR Matsumoto ME Maharjan S Slager SL Vachon CM Cunningham JM Kardia SL 《Human heredity》2011,71(4):221-233
Objective: Our goal was to evaluate the influence of quality control (QC) decisions using two genotype calling algorithms, CRLMM and Birdseed, designed for the Affymetrix SNP Array 6.0. Methods: Various QC options were tried using the two algorithms and comparisons were made on subject and call rate and on association results using two data sets. Results: For Birdseed, we recommend using the contrast QC instead of QC call rate for sample QC. For CRLMM, we recommend using the signal-to-noise rate ≥4 for sample QC and a posterior probability of 90% for genotype accuracy. For both algorithms, we recommend calling the genotype separately for each plate, and dropping SNPs with a lower call rate (<95%) before evaluating samples with lower call rates. To investigate whether the genotype calls from the two algorithms impacted the genome-wide association results, we performed association analysis using data from the GENOA cohort; we observed that the number of significant SNPs were similar using either CRLMM or Birdseed. Conclusions: Using our suggested workflow both algorithms performed similarly; however, fewer samples were removed and CRLMM took half the time to run our 854 study samples (4.2 h) compared to Birdseed (8.4 h). 相似文献
79.
Use of Single-Point Genome Signature Tags as a Universal Tagging Method for Microbial Genome Surveys 下载免费PDF全文
Daniel van der Lelie Celine Lesaulnier Sean McCorkle Joke Geets Safiyh Taghavi John Dunn 《Applied microbiology》2006,72(3):2092-2101
We developed single-point genome signature tags (SP-GSTs), a generally applicable, high-throughput sequencing-based method that targets specific genes to generate identifier tags from well-defined points in a genome. The technique yields identifier tags that can distinguish between closely related bacterial strains and allow for the identification of microbial community members. SP-GSTs are determined by three parameters: (i) the primer designed to recognize a conserved gene sequence, (ii) the anchoring enzyme recognition sequence, and (iii) the type IIS restriction enzyme which defines the tag length. We evaluated the SP-GST method in silico for bacterial identification using the genes rpoC, uvrB, and recA and the 16S rRNA gene. The best distinguishing tags were obtained with the restriction enzyme Csp6I upstream of the 16S rRNA gene, which discriminated all organisms in our data set to at least the genus level and most organisms to the species level. The method was successfully used to generate Csp6I-based tags upstream of the 16S rRNA gene and allowed us to discriminate between closely related strains of Bacillus cereus and Bacillus anthracis. This concept was further used successfully to identify the individual members of a defined microbial community. 相似文献
80.
Li J Marionneau C Koval O Zingman L Mohler PJ Nerbonne JM Anderson ME 《Channels (Austin, Tex.)》2007,1(5):387-394
Mice with genetic inhibition (AC3-I) of the multifunctional Ca(2+)/calmodulin dependent protein kinase II (CaMKII) have improved cardiomyocyte survival after ischemia. Some K(+) currents are up-regulated in AC3-I hearts, but it is unknown if CaMKII inhibition increases the ATP sensitive K(+) current (I(KATP)) that underlies ischemic preconditioning (IP) and confers resistance to ischemia. We hypothesized increased I(KATP) was part of the mechanism for improved ventricular myocyte survival during ischemia in AC3-I mice. AC3-I hearts were protected against global ischemia due to enhanced IP compared to wild type (WT) and transgenic control (AC3-C) hearts. IKATP was significantly increased, while the negative regulatory dose-dependence of ATP was unchanged in AC3-I compared to WT and AC3-C ventricular myocytes, suggesting that CaMKII inhibition increased the number of functional I(KATP) channels available for IP. We measured increased sarcolemmal Kir6.2, a pore-forming I(KATP) subunit, but not a change in total Kir6.2 in cell lysates or single channel I(KATP) opening probability from AC3-I compared to WT and AC3-C ventricles, showing CaMKII inhibition increased sarcolemmal I(KATP) channel expression. There were no differences in mRNA for genes encoding I(KATP) channel subunits in AC3-I, WT and AC3-C ventricles. The I(KATP) opener pinacidil (100 microM) reduced MI area in WT to match AC3-I hearts, while the I(KATP) antagonist HMR1098 (30 microM) increased MI area to an equivalent level in all groups, indicating that increased I(KATP) and augmented IP are important for reduced ischemic cell death in AC3-I hearts. Our study results show CaMKII inhibition enhances beneficial effects of IP by increasing I(KATP). 相似文献