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151.
152.
T lymphocytes arise in the thymus and seed to peripheral lymphoid organs as fully functional cells at the time of exit. In humans, the thymus begins to function very early in ontogeny and releases large numbers of T cells before the time of birth. However, the vast majority of developing thymocytes (>95%) die within the thymus as a result of stringent selection processes. Positive selection imposes self-MHC-restriction on thymocytes and dictates the MHC-restricted repertoire of post-thymic T cells. Negative selection results in deletion of autoreactive cells. Both types of selection depend on cell to cell contracts and on the presence of appropriate growth factors which are still largely undetermined. Cell to cell contacts occur between developing thymocytes and cells of the thymic microenvironment (accessory cells), and are mediated by several receptor/ligand interactions which subserve the function of establishing and stabilizing these contacts. Besides MHC-TCR interactions, adhesion molecules are important for thymocyte maturation, selection and activation, and for the export and peripheral homing of mature T cells produced in the thymus. Here we describe a novel integrin involved in thymocyte-thymic epithelial cell interactions. 相似文献
153.
L Coppola R Giunta R Spiezia V Nappo C Scognamiglio A Tirelli 《Bollettino della Società italiana di biologia sperimentale》1985,61(2):263-270
The increased and irregular post-maximal deflection of the two limbs of thromboelastographic traces has been variably interpreted by the Authors who utilize TEG as a global screening test for haemostasis evaluation. These thromboelastographic patterns have been attributed either to enhanced fibrinolytic activity or to raised clot's rectractility or even to incorrect technique. In our study, 1701 TEG's traces carried out in the last five years have been reviewed in order to evaluate the incidence of such patterns in both healthy subjects and in patients affected by different diseases. The data obtained show that such irregular post-maximal deflection's patterns are quite absence in healthy subjects while reaches a statistically significant incidence only in patients affected by diabetes mellitus, obesity or systemic hypertension. The results seem to suggest that the increased and irregular post-maximal TEG deflection is not a simply product of technique's mistake but may represent an useful index of some haemostatic alterations which need further studies. 相似文献
154.
Nadia Ferlazzo Monica Curr Maria Laura Giunta Domenico Longo Valentina Rizzo Daniela Caccamo Riccardo Ientile 《Amino acids》2020,52(2):171-179
Agmatine, a metabolite generated by arginine decarboxylation, has been reported as neuromodulator and neuroactive substance. Several findings suggest that agmatine displays neuroprotective effects in several models of neurodegenerative disorders, such as Parkinson’s disease (PD). It has been hypothesized that biogenic amines may be involved in neuroprotection by scavenging oxygen radicals, thus preventing the generation of oxidative stress. Mitochondrial dysfunction, that leads to a reduction of oxygen consumption, followed by activation of prolyl hydroxylase and decrease of hypoxia-inducible factor 1 alpha (HIF-1α) levels, has been demonstrated to play a role in PD pathogenesis. Using rotenone-treated differentiated SH-SY5Y cells as the in vitro PD model, we here investigated the molecular mechanisms underlying agmatine neuroprotective effects. Our results showed that the preliminary addition of agmatine induces HIF-1α activation, and prevents the rotenone-induced production of free radical species, and the activation of apoptotic pathways by inhibiting mitochondrial membrane potential decrease and caspase 3 as well as cytochrome c increase. Notably, these effects are mediated by HIF-1α, as indicated by experiments using a HIF-1α inhibitor. The present findings suggest that the treatment with agmatine is able to counteract the neuronal cell injury evoked by mitochondrial toxins. 相似文献
155.
Uschi Lindert Mary Ann Weis Jyoti Rai Frank Seeliger Ingrid Hausser Tosso Leeb David Eyre Marianne Rohrbach Cecilia Giunta 《The Journal of biological chemistry》2015,290(29):17679-17689
Osteogenesis imperfecta (OI) is a heritable connective tissue disease characterized by bone fragility and increased risk of fractures. Up to now, mutations in at least 18 genes have been associated with dominant and recessive forms of OI that affect the production or post-translational processing of procollagen or alter bone homeostasis. Among those, SERPINH1 encoding heat shock protein 47 (HSP47), a chaperone exclusive for collagen folding in the ER, was identified to cause a severe form of OI in dachshunds (L326P) as well as in humans (one single case with a L78P mutation). To elucidate the disease mechanism underlying OI in the dog model, we applied a range of biochemical assays to mutant and control skin fibroblasts as well as on bone samples. These experiments revealed that type I collagen synthesized by mutant cells had decreased electrophoretic mobility. Procollagen was retained intracellularly with concomitant dilation of ER cisternae and activation of the ER stress response markers GRP78 and phospho-eIF2α, thus suggesting a defect in procollagen processing. In line with the migration shift detected on SDS-PAGE of cell culture collagen, extracts of bone collagen from the OI dog showed a similar mobility shift, and on tandem mass spectrometry, the chains were post-translationally overmodified. The bone collagen had a higher content of pyridinoline than control dog bone. We conclude that the SERPINH1 mutation in this naturally occurring model of OI impairs how HSP47 acts as a chaperone in the ER. This results in abnormal post-translational modification and cross-linking of the bone collagen. 相似文献
156.
Baumann M Giunta C Krabichler B Rüschendorf F Zoppi N Colombi M Bittner RE Quijano-Roy S Muntoni F Cirak S Schreiber G Zou Y Hu Y Romero NB Carlier RY Amberger A Deutschmann A Straub V Rohrbach M Steinmann B Rostásy K Karall D Bönnemann CG Zschocke J Fauth C 《American journal of human genetics》2012,90(2):201-216
We report on an autosomal-recessive variant of Ehlers-Danlos syndrome (EDS) characterized by severe muscle hypotonia at birth, progressive scoliosis, joint hypermobility, hyperelastic skin, myopathy, sensorineural hearing impairment, and normal pyridinoline excretion in urine. Clinically, the disorder shares many features with the kyphoscoliotic type of EDS (EDS VIA) and Ullrich congenital muscular dystrophy. Linkage analysis in a large Tyrolean kindred identified a homozygous frameshift mutation in FKBP14 in two affected individuals. Based on the cardinal clinical characteristics of the disorder, four additional individuals originating from different European countries were identified who carried either homozygous or compound heterozygous mutations in FKBP14. FKBP14 belongs to the family of FK506-binding peptidyl-prolyl cis-trans isomerases (PPIases). ER-resident FKBPs have been suggested to act as folding catalysts by accelerating cis-trans isomerization of peptidyl-prolyl bonds and to act occasionally also as chaperones. We demonstrate that FKBP14 is localized in the endoplasmic reticulum (ER) and that deficiency of FKBP14 leads to enlarged ER cisterns in dermal fibroblasts in vivo. Furthermore, indirect immunofluorescence of FKBP14-deficient fibroblasts indicated an altered assembly of the extracellular matrix in vitro. These findings suggest that a disturbance of protein folding in the ER affecting one or more components of the extracellular matrix might cause the generalized connective tissue involvement in this disorder. FKBP14 mutation analysis should be considered in all individuals with apparent kyphoscoliotic type of EDS and normal urinary pyridinoline excretion, in particular in conjunction with sensorineural hearing impairment. 相似文献
157.
Involvement of notch signaling in wound healing 总被引:1,自引:0,他引:1
Chigurupati S Arumugam TV Son TG Lathia JD Jameel S Mughal MR Tang SC Jo DG Camandola S Giunta M Rakova I McDonnell N Miele L Mattson MP Poosala S 《PloS one》2007,2(11):e1167
The Notch signaling pathway is critically involved in cell fate decisions during development of many tissues and organs. In the present study we employed in vivo and cell culture models to elucidate the role of Notch signaling in wound healing. The healing of full-thickness dermal wounds was significantly delayed in Notch antisense transgenic mice and in normal mice treated with gamma-secretase inhibitors that block proteolytic cleavage and activation of Notch. In contrast, mice treated with a Notch ligand Jagged peptide showed significantly enhanced wound healing compared to controls. Activation or inhibition of Notch signaling altered the behaviors of cultured vascular endothelial cells, keratinocytes and fibroblasts in a scratch wound healing model in ways consistent with roles for Notch signaling in wound healing functions all three cell types. These results suggest that Notch signaling plays important roles in wound healing and tissue repair, and that targeting the Notch pathway might provide a novel strategy for treatment of wounds and for modulation of angiogenesis in other pathological conditions. 相似文献
158.
Muscle expressions of MGF, IGF-IEa, and myostatin in intact and hypophysectomized rats: effects of rhGH and testosterone alone or combined 总被引:1,自引:0,他引:1
A E Rigamonti L Locatelli S G Cella S M Bonomo M Giunta F Molinari A Sartorio E E Müller 《Hormones et métabolisme》2009,41(1):23-29
Myostatin and mechano-growth factor (MGF), an isoform of insulin-like growth factor-I (IGF-I), are two important regulators of muscle hypertrophy. The aim of the present study was to investigate the effects of recombinant human growth hormone (rhGH) and/or testosterone on muscle MGF/IGF-IEa/myostatin expression in intact and hypophysectomized rats treated for 15 d with 1) saline or rhGH, 2) sesame oil or testosterone, 3) saline+sesame oil, or rhGH+testosterone (first experiment) or for 7 d with saline or rhGH (second experiment). Animals were killed by decapitation 24 h or 4 d after the last injection (first or second experiment, respectively). Muscle expressions of MGF, IGF-IEa, and myostatin were determined by RT-PCR. A significant increase in the weight of gastrocnemius muscle was observed only in hypophysectomized rats treated with rhGH alone or in combination with testosterone. Administration of rhGH to hypophysectomized rats caused a marked increase in both MGF and IGF-IEa muscle mRNA levels (without any change in the muscle expression of myostatin), an effect that was abolished when testosterone was combined with rhGH. Conversely, in intact rats rhGH increased myostatin muscle mRNA levels without affecting those of MGF and IGF-IEa. Testosterone, alone or combined with rhGH, induced an inhibition of myostatin expression in the muscle of intact rats, but did not change muscle paradigms of hypophysectomized rats. In conclusion, rhGH and/or testosterone anabolic effects in the muscle are mediated by a different expression of MGF/IGF-IEa/myostatin, which is related to the pituitary function. 相似文献
159.
We have investigated the morphological effects of a genetic locus, Pgm1- t,
that affects the expression of a phosphoglucomutase locus (Pgm1) in liver
of rainbow trout (Salmo gairdneri). We have previously shown that embryos
with liver Pgm1 expression hatch earlier than those without liver Pgm1
expression. We predicted that this difference in developmental rate should
cause a reduction in meristic counts in the more rapidly developing fish
with liver Pgm1 expression. Eight meristic (countable) characters in nine
full-sib groups segregating for the presence or absence of liver Pgm1
expression are in agreement with this prediction. In eight of the nine
families, there is a significant difference in the multivariate
distribution of the eight meristic counts between full sibs with and
without liver Pgm1 expression. This separation in multivariate space is
based on a tendency for lower meristic counts in fish with liver Pgm1
expression. The magnitude of these morphological differences is similar to
that between two subspecies of cutthroat trout (Salmo clarki) that show
substantial genetic divergence at structural loci encoding enzymes (Nei's D
= 0.34). These data support the view that small changes in the
developmental process caused by genetic differences at regulatory genes can
have large effects on morphology.
相似文献
160.
C. Delfini E. Pessione E. Garcia Moruno C. Giunta 《Journal of industrial microbiology & biotechnology》1992,11(1):19-22
Summary Must clarification processes cause an increase in the acetate content of wine at the end of the alcoholic fermatation process, this phenomenon being particularly noticeable when fermentation is obtained by means of the so-called high acetate-producer yeast strains. The influence of different must fractions (free run juice, pressed juice, skins and seeds) on acetate production in white grape was investigated, and the addition of skins and and seeds to a synthetic nutritive medium (MNS) was seen to cause a considerable reduction in acetate production. Strain-related differences become evident when the grape bunch is subjected to heat shock (90°C) before musting. In such conditions, acetate content after fermentation is approximately the same as that of the control specimen (not heat treated) for the low acetate-producer strain (S191c) and higher for the high producer strain (S22b). This suggests the presence of some thermolabile factor that is responsible for inhibiting acetate production. In order to determine the chemical nature of this factor, a series of tests was performed on two substances contained in grape skins and seeds, i.e., polyphenolic compounds and unsaturated fatty acids. A reduction in acetate production was observed in the presence of both substances, their effect being greater when used in connection with high acetate-producer yeast strains. 相似文献