全文获取类型
收费全文 | 357篇 |
免费 | 22篇 |
出版年
2022年 | 3篇 |
2021年 | 8篇 |
2020年 | 7篇 |
2019年 | 7篇 |
2018年 | 10篇 |
2017年 | 11篇 |
2016年 | 8篇 |
2015年 | 17篇 |
2014年 | 16篇 |
2013年 | 27篇 |
2012年 | 28篇 |
2011年 | 22篇 |
2010年 | 16篇 |
2009年 | 14篇 |
2008年 | 22篇 |
2007年 | 30篇 |
2006年 | 14篇 |
2005年 | 30篇 |
2004年 | 16篇 |
2003年 | 12篇 |
2002年 | 11篇 |
2001年 | 7篇 |
2000年 | 7篇 |
1999年 | 4篇 |
1995年 | 2篇 |
1993年 | 2篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1987年 | 4篇 |
1986年 | 2篇 |
1984年 | 4篇 |
1983年 | 3篇 |
1980年 | 2篇 |
1974年 | 1篇 |
1970年 | 2篇 |
1969年 | 1篇 |
排序方式: 共有379条查询结果,搜索用时 15 毫秒
51.
Engin F Yao Z Yang T Zhou G Bertin T Jiang MM Chen Y Wang L Zheng H Sutton RE Boyce BF Lee B 《Nature medicine》2008,14(3):299-305
Notch signaling is a key mechanism in the control of embryogenesis. However, its in vivo function during mesenchymal cell differentiation, and, specifically, in bone homeostasis, remains largely unknown. Here, we show that osteoblast-specific gain of Notch function causes severe osteosclerosis owing to increased proliferation of immature osteoblasts. Under these pathological conditions, Notch stimulates early osteoblastic proliferation by upregulating the genes encoding cyclin D, cyclin E and Sp7 (osterix). The intracellular domain of Notch1 also regulates terminal osteoblastic differentiation by directly binding Runx2 and repressing its transactivation function. In contrast, loss of all Notch signaling in osteoblasts, generated by deletion of the genes encoding presenilin-1 and presenilin-2 in bone, is associated with late-onset, age-related osteoporosis, which in turn results from increased osteoblast-dependent osteoclastic activity due to decreased osteoprotegerin mRNA expression in these cells. Together, these findings highlight the potential dimorphic effects of Notch signaling in bone homeostasis and may provide direction for novel therapeutic applications. 相似文献
52.
Jong-Min Kim Yoon-Sung Jung Engin A Sungur Kap-Hoon Han Changyi Park Insuk Sohn 《BMC bioinformatics》2008,9(1):225
Background
Genes interact with each other as basic building blocks of life, forming a complicated network. The relationship between groups of genes with different functions can be represented as gene networks. With the deposition of huge microarray data sets in public domains, study on gene networking is now possible. In recent years, there has been an increasing interest in the reconstruction of gene networks from gene expression data. Recent work includes linear models, Boolean network models, and Bayesian networks. Among them, Bayesian networks seem to be the most effective in constructing gene networks. A major problem with the Bayesian network approach is the excessive computational time. This problem is due to the interactive feature of the method that requires large search space. Since fitting a model by using the copulas does not require iterations, elicitation of the priors, and complicated calculations of posterior distributions, the need for reference to extensive search spaces can be eliminated leading to manageable computational affords. Bayesian network approach produces a discretely expression of conditional probabilities. Discreteness of the characteristics is not required in the copula approach which involves use of uniform representation of the continuous random variables. Our method is able to overcome the limitation of Bayesian network method for gene-gene interaction, i.e. information loss due to binary transformation. 相似文献53.
Balci-Peynircioglu B Waite AL Schaner P Taskiran ZE Richards N Orhan D Gucer S Ozen S Gumucio D Yilmaz E 《Experimental biology and medicine (Maywood, N.J.)》2008,233(11):1324-1333
Familial Mediterranean fever (FMF) is characterized by recurrent attacks of fever and serositis; in some cases, ensuing amyloidosis results in kidney damage. Treatment with colchicine reduces the frequency and severity of FMF attacks and prevents amyloidosis, although the mechanisms behind these effects are unknown. Pyrin, the protein product of the MEFV gene, interacts with ASC, a key molecule in apoptotic and inflammatory processes. ASC forms intracellular speck-like aggregates that presage cell death. Here we show that cell death after ASC speck formation is much slower in nonmyeloid cells than in myeloid cells. Additionally, we demonstrate that colchicine prevents speck formation and show that specks can survive in the extracellular space after cell death. Because we also found that ASC is expressed in renal glomeruli of patients with FMF but not in those of control patients, we posit that high local ASC expression may result in speck formation and that specks from dying cells may persist in the extracellular space where they have the potential (perhaps in association with pyrin) to nucleate amyloid. The fact that speck formation requires an intact microtubule network as shown here could potentially account for the ability of prophylactic colchicine to prevent or reverse amyloidosis in patients with FMF. 相似文献
54.
Transgressive sequences of Campanian-Maastrichtian Stages in Turkey generally begin with medium- to coarse-grained clastics and continue with shallow marine limestones, reefal limestones and then open marine rhythmic fine-grained clastics. These mixed siliciclastic-carbonate sequences are observed on three main platforms known as Rhodope-Pontide (RPP), Anatolide-Tauride (ATP) and Arabian (AP). New species of the rudist genera Gorjanovicia, Radiolites, Sauvagesia, Durania and Sabinia are observed on the RPP. Yvaniella and Ugarella are only found on this platform. Orbitoides gruenbachensis Papp is the most abundant species of benthic foraminifera on the RPP. Cideina soezerii (Sirel), Dizerina anatolica Meriç, Helicorbitoides boluensis Sirel, Ilgazina unilateralis Erdo?an, Nummofallotia kastamonica Özgen-Erdem, Selimina spinalis ?nan, Sirelina orduensis Meriç and ?nan, Smoutina cruysi Drooger are also observed on this platform. Rudist and benthic foraminifera on the ATP have both high diversity and abundance in comparison with RPP and AP faunas. Genus and species diversity of the rudist fauna is quite high: 17 genera and 36 species are described. New rudist genera such as Darendeella, Kurtinia and Balabania and many new species of Radiolitidae and Hippuritidae may be restricted to this platform. Characteristic larger benthic foraminifera contain 18 genera and 37 species. Among benthic foraminifera Loftusia ketini Meriç, L. turcica Meriç and Av?ar, Postomphalocyclus merici ?nan and Pseudoedomia hekimhanensis Görmü? are also likely restricted to this platform. Rudist diversity on the AP is poor. Four endemic genera (Vautrinia, Dictyoptychus, Paracaprinula and Hatayia) and two species (Hippurites syriaca Vautrin, Pironaea syriaca Vautrin) characterize the fauna on this platform. Loftusia diversity and abundance among the benthic foraminifera is quite high. Arnaudella grossouvreii Douvillé, Discyclina schlumbergeri Munier-Chalmas, Loftusia harrisoni Cox, L. elongata Cox, L. matsumaruii Meriç and Görmü? and Pseudorbitolina marthae Douvillé are only documented from southeastern Anatolia. Biogeographic distributions of rudist and benthic foraminifera show different faunal associations on the three main platforms (RPP, ATP and AP). Our data from both rudist and benthic foraminifera indicate that different faunal associations and existence of restricted genera and species may be associated with a deep marine barrier to circulation during the Campanian-Maastrichtian. Southern and northern branches of the Neotethyan Ocean are considered to be barriers in preventing migration of the species. 相似文献
55.
Hülya Akdemir Veysel Süzerer Ahmet Onay Engin Tilkat Yusuf Ersali Yelda Ozden Çiftçi 《Plant Cell, Tissue and Organ Culture》2014,117(1):65-76
Although several studies have been reported on the micropropagation of the pistachio and its rootstocks, to date none of them had been efficient on the mass production of these plants in bioreactor systems. Thus, the micropropagation of juvenile pistachio shoot tips and nodal buds was investigated in a temporary immersion bioreactor system (RITA®) and on a conventional semi-solid medium. Among the tested immersion conditions, immersion for 24 min every 16 h reduced vitrification and improved proliferation in the pistachio. Interactions were evident in immersion time and frequency in nodal segments. Nodal buds were better than shoot tips as the highest multiple shoot formation was recorded in MS medium containing 4 mg L?1 BA and 0.1 mg L?1 GA3 in RITA®. Although shoot tip necrosis (STN) was observed in shoots proliferated on semi-solid MS medium, such a symptom did not occur in shoots sprouted in the RITA®. Additionally, these optimized conditions were applied to nodal buds of mature male pistachio ‘Atl?’ and Pistacia rootstocks (P. khinjuk Stocks and P. atlantica Desf.), and the micropropagation in the bioreactor system, in comparison to the semi-solid medium, was also improved. Furthermore, in vitro rooting of pistachio plantlets, despite the lower range (27.5 %), was also achieved in RITA®. However, rooting was better on semi-solid medium for all tested species (ranged between 50 and 70 %). The results of this study showed that RITA® could be used for the mass propagation of pistachio and its rootstocks, as well as for other woody plant species. 相似文献
56.
Ozaltin F Ibsirlioglu T Taskiran EZ Baydar DE Kaymaz F Buyukcelik M Kilic BD Balat A Iatropoulos P Asan E Akarsu NA Schaefer F Yilmaz E Bakkaloglu A;PodoNet Consortium 《American journal of human genetics》2011,(1):139-147
Idiopathic nephrotic syndrome (INS) is a genetically heterogeneous group of disorders characterized by proteinuria, hypoalbuminemia, and edema. Because it typically results in end-stage kidney disease, the steroid-resistant subtype (SRNS) of INS is especially important when it occurs in children. The present study included 29 affected and 22 normal individuals from 17 SRNS families; genome-wide analysis was performed with Affymetrix 250K SNP arrays followed by homozygosity mapping. A large homozygous stretch on chromosomal region 12p12 was identified in one consanguineous family with two affected siblings. Direct sequencing of protein tyrosine phosphatase receptor type O (PTPRO; also known as glomerular epithelial protein-1 [GLEPP1]) showed homozygous c.2627+1G>T donor splice-site mutation. This mutation causes skipping of the evolutionarily conserved exon 16 (p.Glu854_Trp876del) at the RNA level. Immunohistochemistry with GLEPP1 antibody showed a similar staining pattern in the podocytes of the diseased and control kidney tissues. We used a highly polymorphic intragenic DNA marker-D12S1303-to search for homozygosity in 120 Turkish and 13 non-Turkish individuals in the PodoNet registry. This analysis yielded 17 candidate families, and a distinct homozygous c.2745+1G>A donor splice-site mutation in PTPRO was further identified via DNA sequencing in a second Turkish family. This mutation causes skipping of exon 19, and this introduces a premature stop codon at the very beginning of exon 20 (p.Asn888Lysfs*3) and causes degradation of mRNA via nonsense-mediated decay. Immunohistochemical analysis showed complete absence of immunoreactive PTPRO. Ultrastructural alterations, such as diffuse foot process fusion and extensive microvillus transformation of podocytes, were observed via electron microscopy in both families. The present study introduces mutations in PTPRO as another cause of autosomal-recessive nephrotic syndrome. 相似文献
57.
58.
İhsan Hakkı Ciftci Mehmet Koroglu Engin Karakece 《World journal of microbiology & biotechnology》2014,30(8):2295-2298
In this study, randomized patient sera were used to simultaneously evaluate an automated C-reactive protein (CRP) assay and a commercial semi-automated microCRP assay with respect to correlation, linearity, and accuracy. Patient specimens were analyzed; two independent assay runs were performed on i-CHROMA (Boditech Med Inc., Korea) and IMMAGE 800 (Beckman Coulter Inc., USA) analyzers to estimate the between- and within-run precision. All systems were calibrated, and quality-control materials were analyzed according to the manufacturer’s instructions. The results using the control materials were within the respective manufacturers’ specified limits. The comparison studies were designed using the CLSI EP9-2A guidelines. The mean serum CRP concentrations were 123.2 ± 123.5 mg/L (95 % confidence of interval (CI) 97.9–148.3) using the CRP assay and 130.1 ± 109.3 mg/L (95 % CI 107.9–152.4) using the microCRP assay. The variance values were σ = 15,252.6 and 11,935.8 for the CRP and microCRP assays, respectively. The concordance correlation coefficient value was calculated as 0.8314 (95 % CI 0.7594–0.8833). There was a significant correlation between the CRP and microCRP assays: r = 0.8392 and 95 % CI 0.7675–0.8902 (p < 0.0001). The CRP and microCRP detection methods were well correlated. The i-CHROMA has many advantages over the IMMAGE 800 with respect to space required, analysis time, and system setup/application costs in a laboratory. It may be an attractive instrument for small and intermediate medical centers. 相似文献
59.
Outi Vaarala Arja Vuorela Markku Partinen Marc Baumann Tobias L. Freitag Seppo Meri P?ivi Saavalainen Matti Jauhiainen Rabah Soliymani Turkka Kirjavainen P?ivi Olsen Outi Saarenp??-Heikkil? Juha Rouvinen Merja Roivainen Hanna Nohynek Jukka Jokinen Ilkka Julkunen Terhi Kilpi 《PloS one》2014,9(12)
Background
Narcolepsy results from immune-mediated destruction of hypocretin secreting neurons in hypothalamus, however the triggers and disease mechanisms are poorly understood. Vaccine-attributable risk of narcolepsy reported so far with the AS03 adjuvanted H1N1 vaccination Pandemrix has been manifold compared to the AS03 adjuvanted Arepanrix, which contained differently produced H1N1 viral antigen preparation. Hence, antigenic differences and antibody response to these vaccines were investigated.Methods and Findings
Increased circulating IgG-antibody levels to Pandemrix H1N1 antigen were found in 47 children with Pandemrix-associated narcolepsy when compared to 57 healthy children vaccinated with Pandemrix. H1N1 antigen of Arepanrix inhibited poorly these antibodies indicating antigenic difference between Arepanrix and Pandemrix. High-resolution gel electrophoresis quantitation and mass spectrometry identification analyses revealed higher amounts of structurally altered viral nucleoprotein (NP) in Pandemrix. Increased antibody levels to hemagglutinin (HA) and NP, particularly to detergent treated NP, was seen in narcolepsy. Higher levels of antibodies to NP were found in children with DQB1*06∶02 risk allele and in DQB1*06∶02 transgenic mice immunized with Pandemrix when compared to controls.Conclusions
This work identified 1) higher amounts of structurally altered viral NP in Pandemrix than in Arepanrix, 2) detergent-induced antigenic changes of viral NP, that are recognized by antibodies from children with narcolepsy, and 3) increased antibody response to NP in association of DQB1*06∶02 risk allele of narcolepsy. These findings provide a link between Pandemrix and narcolepsy. Although detailed mechanisms of Pandemrix in narcolepsy remain elusive, our results move the focus from adjuvant(s) onto the H1N1 viral proteins. 相似文献60.
Summary In the mature microspore ofSecale cereale, a set of wall ingrowths deposited as the first (outer) intine layer between exine and the microspore plasma membrane, are revealed by electron microscopy. The wall ingrowths form a girdle in the vicinity of the apertural region at the external pole of microspore which is in contact with the tapetum, so the microspore can be considered as a transfer cell which is polarized. After microspore division the second (inner) intine layer is deposited by the vegetative cell and forms a labyrinth of branched wall ingrowths. As a result, the periphery of a vegetative cell is also irregular and appears as very thin plasmatubules or evaginations delimited by plasma membrane and penetrating the pollen wall.The possible functions of the microspore as a transfer cell and the wall-membrane system of the vegetative cell are discussed. 相似文献