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91.
Two cognate receptors (CRF(1) and CRF(2)) mediate the actions of the stress-regulatory corticotropin-releasing factor (CRF) family of peptides. Defining the respective roles of these receptors in the central nervous system is critical in understanding stress neural circuitry and the development of psychiatric disorders. Here, we examined the role of CRF(2) in several paradigms that assess coping responses to stress. We report that CRF(2) knockout mice responded to a novel setting with increased aggressive behavior toward a bulbectomized conspecific male and show increased immobility during acute swim stress compared with wild-type mice. In addition, CRF(2)-deficient mice exhibited impaired adaptation to isolation stress as evinced by prolonged hypophagia and associated weight loss. Collectively, these results point toward a role for CRF(2) pathways in neural circuits that subserve stress-coping behaviors. 相似文献
92.
Lechapt-Zalcman E Prulière-Escabasse V Advenier D Galiacy S Charrière-Bertrand C Coste A Harf A d'Ortho MP Escudier E 《American journal of physiology. Lung cellular and molecular physiology》2006,290(6):L1277-L1282
In vivo, transforming growth factor (TGF)-beta1 and matrix metalloproteinases (MMPs) present at the site of airway injury are thought to contribute to epithelial wound repair. As TGF-beta1 can modulate MMP expression and MMPs play an important role in wound repair, we hypothesized that TGF-beta1 may enhance airway epithelial repair via MMPs secreted by epithelial cells. We evaluated the in vitro influence of TGF-beta1 on wound repair in human airway epithelial cells cultured under conditions allowing differentiation. The results showed that TGF-beta1 accelerated in vitro airway wound repair, whereas MMP inhibitors prevented this acceleration. In parallel, we examined the effect of TGF-beta1 on the expression of MMP-2 and MMP-9. TGF-beta1 induced a dramatic increase of MMP-2 expression with an increased steady-state level of MMP-2 mRNA, contrasting with a slight increase in MMP-9 expression. To confirm the role of MMP-2, we subsequently evaluated the effect of MMP-2 on in vitro airway wound repair and demonstrated that the addition of MMP-2 reproduced the acceleration of wound repair induced by TGF-beta1. These results strongly suggest that TGF-beta1 increases in vitro airway wound repair via MMP-2 upregulation. It also raises the issue of a different in vivo biological role of MMP-2 and MMP-9 depending on the cytokine microenvironment. 相似文献
93.
Polycystins, calcium signaling, and human diseases 总被引:9,自引:0,他引:9
Delmas P Padilla F Osorio N Coste B Raoux M Crest M 《Biochemical and biophysical research communications》2004,322(4):1374-1383
Autosomal dominant polycystic kidney disease (ADPKD) is a major, inherited nephropathy affecting over 1:1000 of the worldwide population. It is a systemic condition with frequent hepatic and cardiovascular manifestations in addition to the progressive development of fluid-filled cysts from the tubules and collecting ducts of affected kidneys. The pathogenesis of cyst formation is currently thought to involve increased proliferation of epithelial cells, mild dedifferentiation, and fluid accumulation. In the past decade, study of ADPKD led to the discovery of a unique family of highly complex proteins, the polycystins. Loss-of-function mutations in either of two polycystin proteins, polycystin-1 or polycystin-2, give rise to ADPKD. These proteins are thought to function together as part of a multiprotein complex that may initiate Ca2+ signals, directing attention to the regulation of intracellular Ca2+ as a possible misstep that participates in cyst formation. Here we review what is known about the Ca2+ signaling functions of polycystin proteins and focus on findings that have significantly advanced our physiological insight. Special attention is paid to the recently discovered role of these proteins in the mechanotransduction of the renal primary cilium and the model it suggests. 相似文献
94.
Ramstein J Hervouet N Coste F Zelwer C Oberto J Castaing B 《Journal of molecular biology》2003,331(1):101-121
The Escherichia coli histone-like HU protein pool is composed of three dimeric forms: two homodimers, EcHUalpha(2) and EcHUbeta(2), and a heterodimer, EcHUalphabeta. The relative abundance of these dimeric forms varies during cell growth and in response to environmental changes, suggesting that each dimer plays different physiological roles. Here, differential scanning calorimetry and circular dichroism (CD) were used to study the thermal stability of the three E.coli HU dimers and show that each of them has its own thermodynamic signature. Unlike the other HU proteins studied so far, which melt through a single step (N(2)<-->2D), this present thermodynamic study shows that the three E.coli dimers melt according to a two-step mechanism (N(2)<-->I(2)<-->2D). The native dimer, N(2), melts partially into a dimeric intermediate, I(2), which in turn yields the unfolded monomers, D. In addition, the crystal structure of the EcHUalpha(2) dimer has been solved. Comparative thermodynamic and structural analysis between EcHUalpha(2) and the HU homodimer from Bacillus stearothermophilus suggests that the E.coli dimer is constituted by two subdomains of different energetic properties. The CD study indicates that the intermediate, I(2), corresponds to an HU dimer having partly lost its alpha-helices. The partially unfolded dimer I(2) is unable to complex with high-affinity, single-stranded break-containing DNA. These structural, thermodynamic and functional results suggest that the N(2)<-->I(2) equilibrium plays a central role in the physiology of E.coli HU. The I(2) molecular species seems to be the EcHUbeta(2) preferential conformation, possibly related to its role in the E.coli cold-shock adaptation. Besides, I(2) might be required in E.coli for the HU chain exchange, which allows the heterodimer formation from homodimers. 相似文献
95.
Botterel F Cordonnier C Barbier V Wingerstmann L Liance M Coste A Escudier E Bretagne S 《Histology and histopathology》2002,17(4):1095-1101
The role of the airway epithelium in the development of invasive aspergillosis in immunocompromised hosts has rarely been studied although patients at risk for this infection frequently have epithelial damage. We developed an in vitro model of primary culture of human nasal epithelial cells (HNEC) in air-liquid interface, which allows epithelial cell differentiation and mimics in vivo airway epithelium. We subsequently tested 7-day and 24-hour Aspergillus fumigatus filtrates on the apical side of HNEC to know whether A. fumigatus, the main species responsible for invasive aspergillosis, produces specific damage to the epithelial cells. The results were compared with those obtained with non-pathogenic filamentous fungi. Seven-day culture filtrates of A. fumigatus and Penicillium chrysogenum induced electrophysiological modifications whatever the fungus tested. In contrast, only 24-hour A. fumigatus filtrates induced a specific decrease in transepithelial resistance, hyperpolarization of the epithelium, and cytoplasmic vacuolization of HNEC compared with both A. niger and Penicillium chrysogenum. The inhibition of the A. fumigatus effects with amiloride suggests that the 24-hour fungal filtrate acts through sodium channels of HNEC. These early modifications of the epithelial cells could facilitate colonization of the airways by A. fumigatus. To know whether the molecules involved are specific to A. fumigatus or simply produced more rapidly than by other filamentous fungi warrants further investigation. In this perspective, the primary culture of HNEC represents a suitable model to study the interactions between airway epithelial cells and A. fumigatus. 相似文献
96.
Arnaud Morel Nadine Fernandez A. de La Coste Hédi Haddada Mireille Viguier Barbara S. Polla Bénédicte Antoine A. Kahn 《Cancer immunology, immunotherapy : CII》1998,46(5):277-282
The use of gene-modified tumor cells as a strategy for active immunotherapy is currently undergoing intensive fundamental
and clinical research. Most clinical trials use γ-ray-irradiated tumor cells as vaccine, although little is known about the
effects of irradiation on the immunogenicity of tumor cells. In particular, no data have been reported so far concerning the
effects of γ-ray irradiation on the expression of B7 molecules in tumor cells. In this paper, we show a neoexpression of the
B7.1 molecule after γ-ray irradiation in tumor cell lines from different tissues, while the B7.2 molecule remains unexpressed
in all the cell lines tested. Furthermore, the induction of B7.1 molecule membrane expression after irradiation is shown to
result from the neoexpression of B7.1 mRNA, and to be reproduced with H2O2 oxidative stress. These data could explain the enhanced immunogenicity of many tumor cells after irradiation, and could lead
to new immunotherapy protocols.
Received: 27 November 1997 / Accepted: 26 February 1998 相似文献
97.
CM Galmarini A Kertesz R Oliva J Porta F C Galmarini 《Cancer immunology, immunotherapy : CII》1998,15(4):282-285
Bone metastasis in the hand is rare. The etiology is quite different from that of metastasis to other bones; bronchogenic
carcinoma is by far the most frequent case. Distal phalanges are mainly involved with irregular osteolysis and cortical destruction.
Differential diagnosis of phalangeal metastasis includes osteomyelitis, rheumatoid arthritis and gout. The prognosis is always
that of metastatic bronchial cancer with an average survival of three months. Treatment may involve distal digital amputation
or antalgic radiotherapy. A case of bronchogenic carcinoma with metastasis to the thumb is presented. The metastasis was located
in the distal phalanx of the left thumb. The primary tumor was located in the lung. Treatment consisted of amputation. The
overall survival was five months. 相似文献
98.
Microsatellite variation in Drosophila melanogaster and Drosophila simulans: a reciprocal test of the ascertainment bias hypothesis 总被引:2,自引:1,他引:1
Interspecific comparisons of microsatellite loci have repeatedly shown that
the loci are longer and more variable in the species from which they are
derived (the focal species) than are homologous loci in other (nonfocal)
species. There is debate as to whether this is due to directional evolution
or to an ascertainment bias during the cloning and locus selection
processes. This study tests these hypotheses by performing a reciprocal
study. Eighteen perfect dinucleotide microsatellite loci identified from a
Drosophila simulans library screen and 18 previously identified in an
identical Drosophila melanogaster library screen were used to survey
natural populations of each species. No difference between focal and
nonfocal species was observed for mean PCR fragment length. However,
heterozygosity and number of alleles were significantly higher in the focal
species than in the nonfocal species. The most common allele in the
Zimbabwe population of both species was sequenced for 31 of the 36 loci.
The length of the longest stretch of perfect repeat units is, on average,
longer in the focal species than in the non-focal species. There is a
positive correlation between the length of the longest stretch of perfect
repeats and heterozygosity. The difference in heterozygosity can thus be
explained by a reduction in the length of the longest stretch of perfect
repeats in the nonfocal species. Furthermore, flanking-sequence length
difference was noted between the two species at 58% of the loci sequenced.
These data do not support the predictions of the directional-evolution
hypothesis; however, consistent with the ascertainment bias hypothesis, the
lower variability in nonfocal species is an artifact of the microsatellite
cloning and isolation process. Our results also suggest that the magnitude
of ascertainment bias for repeat unit length is a function of the
microsatellite size distribution in the genomes of different species.
相似文献
99.
Prospects for estimating nucleotide divergence with RAPDs 总被引:11,自引:0,他引:11
The technique of random amplification of polymorphic DNA (RAPD), which is
simply polymerase chain reaction (PCR) amplification of genomic DNA by a
single short oligonucleotide primer, produces complex patterns of anonymous
polymorphic DNA fragments. The information provided by these banding
patterns has proved to be of great utility for mapping and for verification
of identity of bacterial strains. Here we consider whether the degree of
similarity of the banding patterns can be used to estimate nucleotide
diversity and nucleotide divergence. With haploid data, fragments generated
by RAPD-PCR can be treated in a fashion very similar to that for
restriction-fragment data. Amplification of diploid samples, on the other
hand, requires consideration of the fact that presence of a band is
dominant to absence of the band. After describing a method for estimating
nucleotide divergence on the basis of diploid samples, we summarize the
restrictions and criteria that must be met when RAPD data are used for
estimating population genetic parameters.
相似文献
100.