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81.
Rosalba Lepore Andriy Kryshtafovych Markus Alahuhta Harshul A. Veraszto Yannick J. Bomble Joshua C. Bufton Alex N. Bullock Cody Caba Hongnan Cao Owen R. Davies Ambroise Desfosses Matthew Dunne Krzysztof Fidelis Celia W. Goulding Manickam Gurusaran Irina Gutsche Christopher J. Harding Marcus D. Hartmann Christopher S. Hayes Andrzej Joachimiak Petr G. Leiman Peter Loppnau Andrew L. Lovering Vladimir V. Lunin Karolina Michalska Ignacio Mir-Sanchis AK Mitra John Moult George N. Phillips Jr Daniel M. Pinkas Phoebe A. Rice Yufeng Tong Maya Topf Jonathan D. Walton Torsten Schwede 《Proteins》2019,87(12):1037-1057
The functional and biological significance of selected CASP13 targets are described by the authors of the structures. The structural biologists discuss the most interesting structural features of the target proteins and assess whether these features were correctly reproduced in the predictions submitted to the CASP13 experiment. 相似文献
82.
Spontaneous calcification process in primary renal cells from a medullary sponge kidney patient harbouring a GDNF mutation 下载免费PDF全文
Federica Mezzabotta Rosalba Cristofaro Monica Ceol Dorella Del Prete Giovanna Priante Alessandra Familiari Antonia Fabris Angela D'Angelo Giovanni Gambaro Franca Anglani 《Journal of cellular and molecular medicine》2015,19(4):889-902
Medullary nephrocalcinosis is a hallmark of medullary sponge kidney (MSK). We had the opportunity to study a spontaneous calcification process in vitro by utilizing the renal cells of a patient with MSK who was heterozygous for the c.‐27 + 18G>A variant in the GDNF gene encoding glial cell‐derived neurotrophic factor. The cells were obtained by collagenase digestion of papillary tissues from the MSK patient and from two patients who had no MSK or nephrocalcinosis. These cells were typed by immunocytochemistry, and the presence of mineral deposits was studied using von Kossa staining, scanning electron microscopy analysis and an ALP assay. Osteoblastic lineage markers were studied using immunocytochemistry and RT‐PCR. Staminality markers were also analysed using flow cytometry, magnetic cell separation technology, immunocytochemistry and RT‐PCR. Starting from p2, MSK and control cells formed nodules with a behaviour similar to that of calcifying pericytes; however, Ca2PO4 was only found in the MSK cultures. The MSK cells had morphologies and immunophenotypes resembling those of pericytes or stromal stem cells and were positive for vimentin, ZO1, αSMA and CD146. In addition, the MSK cells expressed osteocalcin and osteonectin, indicating an osteoblast‐like phenotype. In contrast to the control cells, GDNF was down‐regulated in the MSK cells. Stable GDNF knockdown was established in the HK2 cell line and was found to promote Ca2PO4 deposition when the cells were incubated with calcifying medium by regulating the osteonectin/osteopontin ratio in favour of osteonectin. Our data indicate that the human papilla may be a perivascular niche in which pericyte/stromal‐like cells can undergo osteogenic differentiation under particular conditions and suggest that GDNF down‐regulation may have influenced the observed phenomenon. 相似文献
83.
信息素是生物体向外释放的化学物质,在细胞及生物体中具有种内信息传递的生理学功能。信息素这一类分子广泛分布于系统发生史中,它们的特异活性在单细胞生物、昆虫以及脊椎动物中均有报道。脊椎动物中信息素的信号传输已被证实是一嗅觉依赖过程,7TM-受体被认为是信号传输过程中的信号转换器。在低等单细胞生物(例如:来可夫游仆虫)的细胞膜上存在有信息素异构体,作为信息素分子的有效结合位点而行使其功能。本研究主要探讨单细胞的信息素(Er-1和Er-2)的基础细胞生理学作用是仅限于产生该信息素的物种,还是对其它的原生动物(例如:四膜虫)或对系统发育中分类地位较高的细胞(例如:MRC5成纤维细胞或J774巨噬细胞)均具有调节活性。研究结果表明,游仆虫的两种信息素对梨形四膜虫GL的生长调节有显著不同的作用:当信息素浓度为10-11M时,Er-1具有正调控作用,而Er-2具有抑制剂的作用。这两种配体的趋化作用也有很不同:Er-1具有一种广范的化学排斥特性,而Er-2具有一个双峰的化学吸引剂的性质。计算机检测发现,与Er-2的作用不同,Er-1可略微降低被测细胞的游动速率。趋化现象的选择特性表明Er-2信息素的受体有一种“短期”的特性;而Er-1是不能选择任何亚种群的,这也支持了我们先前的研究数据,即这两种信息素在四膜虫GL内产生两种不同的信号。四膜虫对信息素特异性的反应表明四膜虫能辨别非常近似但带有微小差异的配体(如Er-1和Er-2的电荷差异)。 相似文献
84.
Cassandrini D Calevo MG Tessa A Manfredi G Fattori F Meschini MC Carrozzo R Tonoli E Pedemonte M Minetti C Zara F Santorelli FM Bruno C 《Biochemical and biophysical research communications》2006,342(2):387-393
Determination of mitochondrial DNA (mtDNA) heteroplasmy for the diagnosis of patients with mitochondrial disorders is a difficult task due to the coexistence of wild-type and mutant genomes. We have developed a new method for genotyping and quantification of heteroplasmic point mutations in mtDNA based on the SNaPshot technology. We compared the data of this method with the widely used "last hot-cycle" PCR-RFLP method by studying 15 patients carrying mtDNA mutations. We showed that SNaPshot is an accurate, reproducible, and sensitive technique for the determination of heteroplasmic mtDNA mutations in different tissues from patients, and it is a promising system to be used in prenatal and postnatal diagnosis of mtDNA-associated disorders. 相似文献
85.
Ornella Piazza Simona Cotena Edoardo De Robertis Ferdinando Caranci Rosalba Tufano 《Neurochemical research》2009,34(7):1289-1292
The pathogenesis of sepsis associated encephalopathy (SAE) is not yet clear: the blood–brain barrier (BBB) disruption has
been indicated among the possible causative mechanisms. S100B, a calcium binding protein, originates in the central nervous
system but it can be also produced by extra-cerebral sources; it is passively released from damaged glial cells and neurons;
it has limited passage through the BBB. We aimed to demonstrate BBB damage as part of the pathogenesis of SAE by cerebral
spinal fluid (CSF) and serum S100B measurements and by magnetic resonance imaging (MRI). This paper describes four septic
patients in whom SAE was clinically evident, who underwent MRI and S100B measurement. We have not found any evidence of CSF-S100B
increase. Serum S100B increase was found in three out of four patients. MRI did not identify images attributable to BBB disruption
but vasogenic edema, probably caused by an alteration of autoregulation, was diagnosed. S100B does not increase in CSF of
septic patients; S100B increase in serum may be due to extracerebral sources and does not prove any injury of BBB. MRI can
exclude other cerebral pathologies causing brain dysfunction but is not specific of SAE. BBB damage may be numbered among
the contributors of SAE, which aetiology is certainly multifactorial: an interplay between the toxic mediators involved in
sepsis and the indirect effects of hyperthermia, hypossia and hypoperfusion. 相似文献
86.
This study shows the effects of the flavonoid quercetin on diverse mitochondrial functions, among them membrane permeability.
Our findings indicate that the addition of 50 μM quercetin did not produce reactive oxygen derived species; however, it inhibited
the oxidative stress induced after the addition of Fe2/H2O2 by about 38%. At this concentration, quercetin also promoted a fast calcium release, inhibited oxidative phosphorylation,
stimulated oxygen consumption, and decreased membrane potential. In addition 50 μM quercetin inhibited the adenine nucleotide
translocase (ANT) by 46%. These effects induced the opening of the permeability transition pore and release of cytochrome
c, by its interaction with a component of the non-specific pore complex, fixed to the carrier in the conformation c, as carboxyatractyloside
does. Quercetin-induced permeability transition pore opening was inhibited by 0.5 μM cyclosporin A, but, interestingly, the
release of cytochrome c was not inhibited by the immunosuppressor, as quercetin was found to disrupt the outer membrane. 相似文献
87.
Siew Ping Han Lexie R. Friend John H. Carson George Korza Elisa Barbarese Michael Maggipinto Jodie T. Hatfield Joseph A. Rothnagel Ross Smith 《Traffic (Copenhagen, Denmark)》2010,11(7):886-898
Trafficking of mRNA molecules from the nucleus to distal processes in neural cells is mediated by heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 trans‐acting factors. Although hnRNP A2/B1 is alternatively spliced to generate four isoforms, most functional studies have not distinguished between these isoforms. Here, we show, using isoform‐specific antibodies and isoform‐specific green fluorescent protein (GFP)‐fusion expression constructs, that A2b is the predominant cytoplasmic isoform in neural cells, suggesting that it may play a key role in mRNA trafficking. The differential subcellular distribution patterns of the individual isoforms are determined by the presence or absence of alternative exons that also affect their dynamic behavior in different cellular compartments, as measured by fluorescence correlation spectroscopy. Expression of A2b is also differentially regulated with age, species and cellular development. Furthermore, coinjection of isoform‐specific antibodies and labeled RNA into live oligodendrocytes shows that the assembly of RNA granules is impaired by blockade of A2b function. These findings suggest that neural cells modulate mRNA trafficking by regulating alternative splicing of hnRNP A2/B1 and controlling expression levels of A2b, which may be the predominant mediator of cytoplasmic‐trafficking functions. These findings highlight the importance of considering isoform‐specific functions for alternatively spliced proteins. 相似文献
88.
Tritto P Specchia V Fanti L Berloco M D'Alessandro R Pimpinelli S Palumbo G Bozzetti MP 《Genetica》2003,117(2-3):247-257
The crystal–Stellate system is one of the most known example of interaction between heterochromatin and euchromatin: a heterochromatic locus on the Y chromosome (crystal) 'represses a euchromatic locus (Stellate) on the X chromosome in Drosophila melanogaster. The molecular mechanism regulating this interaction is not completely understood. It is becoming clear that an RNA interference (RNAi) mechanism could be responsible for the silencing carried out by crystal on the Stellate sequences. Here, a detailed structural analysis of all the sequences involved in the system is reported, demonstrating a their 'puzzling structure. In addition three autosomal mutations: sting, scratch and sirio are described that interfere with the system. All of them are male sterile mutations and exhibit crystals made by the STELLATE protein in their primary spermatocytes. They are requested during oogenesis and early in embryogenesis as well. Hypothesis on the involvement of these genes in activating the Stellate sequences are discussed. 相似文献
89.
Vigetti D Binelli G Monetti C Prati M Bernardini G Gornati R 《Journal of molecular evolution》2003,57(6):650-658
During vertebrate evolution, the uric acid degradation pathway has been modified and several enzymes have been lost. Consequently, the end product of purine catabolism varies from species to species. In the past few years, we have focused our attention on vertebrate allantoicase (an uricolytic pathway enzyme), whose activity is present in certain fish and amphibians only, but whose mRNA we detected also in mammals. As allantoicase activity disappeared in amniotes, we wonder why these sequences not only remain present in the mammalian genome, but are still transcribed. To elucidate this issue, we have cloned and analyzed comparable cDNA sequences of different organisms from ascidians to mammals. The analysis of the nonsynonymous–synonymous substitution rate that we performed on the coding region comprising exons 3 to 8 by means of maximum likelihood suggested that a certain amount of purifying selection is acting on the allantoicase sequences. Some implications of the preservation of an apparently unnecessary gene in higher vertebrates are discussed. 相似文献
90.
Carruba G D'Agostino P Miele M Calabrò M Barbera C Bella GD Milano S Ferlazzo V Caruso R Rosa ML Cocciadiferro L Campisi I Castagnetta L Cillari E 《Journal of cellular biochemistry》2003,90(1):187-196
We have investigated the effects of sex steroids, estradiol (E2), and testosterone (T) on the synthesis of tumor necrosis factor alpha (TNF-alpha) and interleukin-10 (IL-10) in phorbol-myristate-acetate (PMA)-differentiated human monoblastic U937 cells. The ability of both hormones to modulate the viability and programmed cell death of macrophage-like PMA-differentiated U937 cells was also inspected. E2 increased TNF-alpha synthesis, whereas T had no effect on the production of this cytokine. The combination of E2 and its antagonist tamoxifen or ICI-182,789 completely abolished the induction of TNF-alpha, while combination of T and its antagonist Casodex (CSDX) did not significantly affect TNF-alpha production by U937 cells. Exposure of cells to E2 resulted in a dose-dependent decrease of IL-10 synthesis, while again T did not show any detectable effect. In addition, E2 induced a significant increase of apoptosis in macrophage-like U937 cells and this increase was inhibited by the simultaneous addition of either tamoxifen or ICI-182. In contrast, T alone or in combination with CSDX did not modify apoptotic rates of U937 cells. This evidence, taken together, suggests that estrogens, but not androgens, exert a pro-inflammatory action through the modulation of TNF-alpha and IL-10, and regulate the immune effector cells by the induction of programmed cell death. 相似文献