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101.
Basile M Lin R Kabbani N Karpa K Kilimann M Simpson I Kester M 《Archives of biochemistry and biophysics》2006,446(1):60-68
Paralemmin is a novel lipid-anchored protein, which is highly expressed in neuronal plasma membranes. In this study, we demonstrate that paralemmin specifically interacts with the third intracellular loop of the D3 dopamine receptor. Utilizing co-immunoprecipitation and glutathione-S-transferase (GST) pulldown strategies, we demonstrate that paralemmin interacts exclusively with D3, but not D2 or D4 dopamine receptors or beta-adrenergic receptors. Immunocytochemistry demonstrated co-localization of paralemmin and D3 receptor in vivo in hippocampus and cerebellum and in vitro in glial and neuronal cultures. Deletion mutational analysis indicates that amino acids 154-230 of paralemmin strongly interacted with amino acids 211-227 and 281-330 of the third intracellular loop of D3 receptor. The consequences of these interactions were investigated by co-expression in HEK293 cells. Cell surface biotinylation experiments demonstrate that paralemmin decreased D3 receptor concentration at the plasma membrane. Consistent with this observation, paralemmin expression decreased dopamine-stimulated adenylate cyclase activity. However, paralemmin also decreased basal, isoproterenol and forskolin-stimulated adenylate cyclase activity, suggesting a more general cellular function for paralemmin. Taken together, paralemmin has been implicated as a potent modulator of cellular cAMP signaling within the brain. 相似文献
102.
Nicoletta Bodrato Luisa Franco Chiara Fresia Lucrezia Guida Cesare Usai Annalisa Salis Iliana Moreschi Chiara Ferraris Claudia Verderio Giovanna Basile Santina Bruzzone Sonia Scarf�� Antonio De Flora Elena Zocchi 《The Journal of biological chemistry》2009,284(22):14777-14787
Abscisic acid (ABA) is a phytohormone regulating important functions in
higher plants, notably responses to abiotic stress. Recently, chemical or
physical stimulation of human granulocytes was shown to induce production and
release of endogenous ABA, which activates specific cell functions. Here we
provide evidence that ABA stimulates several functional activities of the
murine microglial cell line N9 (NO and tumor necrosis factor-α
production, cell migration) through the second messenger cyclic ADP-ribose and
an increase of intracellular calcium. ABA production and release occur in N9
cells stimulated with bacterial lipopolysaccharide, phorbol myristate acetate,
the chemoattractant peptide f-MLP, or β-amyloid, the primary plaque
component in Alzheimer disease. Finally, ABA priming stimulates N9 cell
migration toward β-amyloid. These results indicate that ABA is a
pro-inflammatory hormone inducing autocrine microglial activation, potentially
representing a new target for anti-inflammatory therapies aimed at limiting
microglia-induced tissue damage in the central nervous system.Microglial cells are the monocyte/macrophage equivalent of the central
nervous system and represent the first line of defense in the brain, by
removing infectious agents and damaged cells
(1). Microglia can also release
a variety of trophic factors and cytokines able to regulate the communication
between neuronal and other glial cells and can contribute to tissue repair and
neuroprotection
(2–4).
Pathologic microglial activation, however, confers neurotoxic properties to
these cells, thereby causing neuronal degeneration
(5). Excessive activation of
microglia, under conditions of chronic inflammation, can contribute to the
pathogenesis of neurodegenerative diseases, such as multiple sclerosis and
Alzheimer and Parkinson diseases, by producing and releasing a number of
potentially cytotoxic substances, including pro-inflammatory cytokines and NO
(4,
6–8).
Therefore, identification of the molecular mechanisms underlying microglial
activation might lead to the development of new anti-inflammatory drugs for
the treatment of these diseases.Abscisic acid
(ABA)2 is a plant
hormone regulating important biological functions in higher plants, including
response to abiotic stress, control of stomatal closure, regulation of seed
dormancy, and germination (9).
Recently, ABA was shown to behave as an endogenous pro-inflammatory hormone in
human granulocytes (10),
stimulating several functional activities of these cells (migration,
phagocytosis, reactive oxygen species, and NO production) through a signaling
cascade that involves a protein kinase A-mediated ADP-ribosyl cyclase
phosphorylation and consequent overproduction of the universal Ca2+
mobilizer cyclic ADP-ribose (cADPR)
(11). This mechanism leads to
an increase of the intracellular Ca2+ concentration, which is
ultimately responsible for granulocyte activation
(10).The facts that microglial cells play a defensive role in the central
nervous system similar to that of granulocytes in other tissues and that cADPR
has been described as the second messenger involved in the activation of
microglia induced by lipopolysaccharide (LPS)
(12) prompted us to
investigate the effect of ABA in these cells.Indeed, exogenous ABA, at concentrations ranging from 250 nm to
20 μm, elicits functional activation of murine N9 cells,
stimulating TNF-α release and cell migration through activation of the
ADP-ribosyl cyclase CD38 and overproduction of cADPR. Moreover, N9 cells
produce and release ABA when stimulated with LPS, amyloid β-peptide
(βA), phorbol myristate acetate (PMA), or the chemoattractant peptide
f-MLP. These results indicate that ABA behaves as an endogenous,
pro-inflammatory hormone in murine microglia and provide a new target for
future investigations into the role of this hormone in inflammatory and
degenerative diseases of the central nervous system accompanied by microglial
activation. 相似文献
103.
The last decades evidenced auditory laterality in vertebrates, offering new important insights for the understanding of the origin of human language. Factors such as the social (e.g. specificity, familiarity) and emotional value of sounds have been proved to influence hemispheric specialization. However, little is known about the crossed effect of these two factors in animals. In addition, human-animal comparative studies, using the same methodology, are rare. In our study, we adapted the head turn paradigm, a widely used non invasive method, on 8–9-year-old schoolgirls and on adult female Campbell''s monkeys, by focusing on head and/or eye orientations in response to sound playbacks. We broadcast communicative signals (monkeys: calls, humans: speech) emitted by familiar individuals presenting distinct degrees of social value (female monkeys: conspecific group members vs heterospecific neighbours, human girls: from the same vs different classroom) and emotional value (monkeys: contact vs threat calls; humans: friendly vs aggressive intonation). We evidenced a crossed-categorical effect of social and emotional values in both species since only “negative” voices from same class/group members elicited a significant auditory laterality (Wilcoxon tests: monkeys, T = 0 p = 0.03; girls: T = 4.5 p = 0.03). Moreover, we found differences between species as a left and right hemisphere preference was found respectively in humans and monkeys. Furthermore while monkeys almost exclusively responded by turning their head, girls sometimes also just moved their eyes. This study supports theories defending differential roles played by the two hemispheres in primates'' auditory laterality and evidenced that more systematic species comparisons are needed before raising evolutionary scenario. Moreover, the choice of sound stimuli and behavioural measures in such studies should be the focus of careful attention. 相似文献
104.
A variety of recombinant protein expression systems have been developed for heterologous genes in both prokaryotic and eukaryotic
systems such as bacteria, yeast, mammals, insects, transgenic animals, and plants. Recently Leishmania tarentolae, a trypanosomatid protozoan parasite of the white-spotted wall gecko (Tarentola annularis), has been suggested as candidate for heterologous genes expression. Trypanosomatidae are rich in glycoproteins, which can
account for more than 10% of total protein; the oligosaccharide structures are similar to those of mammals with N-linked galactose,
and fucose residues. To date several heterologous proteins have been expressed in L. tarentolae including both cytoplasmic enzymes and membrane receptors. Significant advances in the development of new strains and vectors,
improved techniques, and the commercial availability of those tools coupled with a better understanding of the biology of
Leishmania species will lead to value and power in commercial and research labs alike. 相似文献
105.
Giovanni Ligresti Loredana Militello Linda S. Steelman Andrea Cavallaro Francesco Basile Ferdinando Nicoletti Franca Stivala James A. McCubrey Massimo Libra 《Cell cycle (Georgetown, Tex.)》2009,8(9):1352-1358
Phosphatidylinositol 3-kinases (PI3Ks) are a group of lipid kinases that regulate signaling pathways involved in cell proliferation, adhesion, survival and motility. The PI3K pathway is considered to play an important role in tumorigenesis. Activating mutations of the p110α subunit of PI3K (PIK3CA) have been identified in a broad spectrum of tumors. Analyses of PIK3CA mutations reveals that they increase the PI3K signal, stimulate downstream Akt signaling, promote growth factor-independent growth and increase cell invasion and metastasis. In this review, we analyze the contribution of the PIK3CA mutations in cancer, and their possible implications for diagnosis and therapy. 相似文献
106.
Christophe Mésangeau Basile Pérès Carole Descamps-François Philippe Chavatte Valérie Audinot Sophie Coumailleau Jean A. Boutin Philippe Delagrange Caroline Bennejean Pierre Renard Daniel H. Caignard Pascal Berthelot Saïd Yous 《Bioorganic & medicinal chemistry》2010,18(10):3426-3436
Novel heterodimer analogues of melatonin were synthesized, when agomelatine (1) and various aryl units are linked via a linear alkyl chain through the methoxy group. The compounds were tested for their actions at melatonin receptors. Several of these ligands are MT1-selective with nanomolar or subnanomolar affinity. In addition, while most of the derivatives behave as partial agonists on one or both receptor subtypes, N-[2-(7-{4-[6-(1-methoxycarbonylethyl)naphthalen-2-yloxy]butoxy}naphthalen-1-yl)ethyl]acetamide (36), a subnanomolar MT1 ligand with an 11-fold preference over MT2 receptors, is a full antagonist on both receptors. Our results also confirm that the selectivity seen for the MT1 receptor arises predominantly from steric factors and is not a consequence of the bridging of melatonin receptor dimers. 相似文献
107.
Maullu C Lampis G Basile T Ingianni A Rossolini GM Pompei R 《Journal of applied microbiology》1999,86(2):182-186
Cheese whey and cottage cheese whey are by-products of the milk and cheese industry, resulting from the production of cheese and cottage cheese (ricotta) from milk. They are still rich in organic substances and cannot be discarded into the environment without proper treatment. Whey and cottage cheese whey were used as culture media for some strains of the yeast Kluyveromyces lactis, transformed with the human lysozyme gene. It was found that the yeast strains grew well in both media and produced a considerable amount of recombinant protein. Production kinetics showed that the human lysozyme was produced in a greater amount within 36 h of fermentation (125 micrograms ml-1 vs 25 micrograms ml-1 in the control) than in the synthetic commercial media used for strain preparation and characterization. The recombinant protein produced was actually shown to be the human lysozyme, using renaturing SDS-PAGE and Western blot techniques. While producing recombinant protein, the Kluyveromyces strain cleared the cottage cheese whey of most organic substances and produced a considerable amount (almost 3%) of lysozyme-enriched useful biomass. 相似文献
108.
Yamada M Basile AS Fedorova I Zhang W Duttaroy A Cui Y Lamping KG Faraci FM Deng CX Wess J 《Life sciences》2003,74(2-3):345-353
Until recently, little was known about the possible physiological functions of the M(5) muscarinic acetylcholine receptor subtype, the last member of the muscarinic receptor family (M(1)-M(5)) to be cloned. To learn more about the potential physiological roles of this receptor subtype, we generated and analyzed M(5) receptor-deficient mice (M5 -/- mice). Strikingly, acetylcholine, a potent dilator of most vascular beds, virtually lost the ability to dilate cerebral arteries and arterioles in M5 -/- mice, suggesting that endothelial M(5) receptors mediate this activity in wild-type mice. This effect was specific for cerebral blood vessels, since acetylcholine-mediated dilation of extra-cerebral arteries remained fully intact in M5 -/- mice. In addition, in vitro neurotransmitter release experiments indicated that M(5) receptors located on dopaminergic nerve terminals play a role in facilitating muscarinic agonist-induced dopamine release in the striatum, consistent with the observation that the dopaminergic neurons innervating the striatum almost exclusively express the M(5) receptor subtype. We also found that the rewarding effects of morphine, the prototypical opiate analgesic, were substantially reduced in M5 -/- mice, as measured in the conditioned place preference paradigm. Furthermore, both the somatic and affective components of naloxone-induced morphine withdrawal symptoms were significantly attenuated in M5 -/- mice. It is likely that these behavioral deficits are caused by the lack of mesolimbic M(5) receptors, activation of which is known to stimulate dopamine release in the nucleus accumbens. These results convincingly demonstrate that the M(5) muscarinic receptor is involved in modulating several important pharmacological and behavioral functions. These findings may lead to novel therapeutic strategies for the treatment of drug addiction and certain cerebrovascular disorders. 相似文献
109.
Gangemi S Basile G Merendino RA Epifanio A Di Pasquale G Ferlazzo B Nicita-Mauro V Morgante L 《Mediators of inflammation》2003,12(4):251-253
Parkinson's disease (PD) is an extra-pyramidal neurodegenerative disorder, in which alterations of the immune system are involved. Interleukin (IL)-15 stimulates cellular immune response and induces growth and differentiation of various immune cells. RANTES, promoting leukocyte infiltration to sites of inflammation, mediates the trafficking and homing of immune cells. To clarify the potential effect of levodopa on the immunological network of PD, we analyzed IL-15 and RANTES serum levels in PD patients, treated or not with levodopa, and in healthy donors. Levodopa-treated patients showed significantly higher IL-15 and RANTES circulating levels with respect to healthy controls and higher, although not significantly, levels with respect to untreated patients. So, we hypothesize that the immunological alterations found in PD may be linked, at least in part, to levodopa therapy. 相似文献
110.
Basile AS 《Neurochemistry international》2002,41(2-3):115-122
Experimental evidence indicates that ammonia causes neuroexcitation and seizures. This contrasts with the lethargy, confusion and other manifestations of global CNS depression commonly considered to be major components of hyperammonemic encephalopathies. Substantial data now indicates that ammonia can modulate GABAergic neurotransmission through direct and indirect mechanisms. This modulation consists of an enhancement of GABAergic neurotransmission at concentrations commonly encountered in hyperammonemic states and precedes the suppression of inhibitory neuronal function observed at higher (>1mM) ammonia concentrations. Not only is this increase in GABAergic neurotransmission consistent with the clinical picture of lethargy, ataxia and cognitive deficits associated with liver failure and congenital hyperammonemia, but it also provides a mechanism for testing new therapeutic modalities for the treatment of hyperammonemic encephalopathy. 相似文献