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11.
12.
Massimo Di Giulio 《Journal of molecular evolution》1997,45(6):571-578
A highly complex RNA world, as is sometimes presented in view of the widespread and diversified use of RNA enzymes, would
have encountered many difficulties in passing to a world with catalysis mediated by proteins. These difficulties can be overcome
by postulating a very early relationship between the nucleotide and the amino acid components. In particular, after asserting
that some characteristics expressed by (nucleotide) coenzymes in catalysis are easier to understand if a close and early relationship
between these coenzymes and amino acids is hypothesized, a model is presented for the origin of the enzyme–coenzyme complex.
This model is essentially based on an intermediate formed by a tRNA-like molecule covalently linked to a polypeptide. The
model attributes the majority of the catalytic role in the ribonucleoprotein world to the latter complex and thus it takes
into account the birth of the key intermediate in the origin of protein synthesis—namely, peptidyl-tRNA, which would have
otherwise been extremely difficult to select. The predictions of the model are discussed along with its robustness, using
the data derived from the study of intermediary metabolism and those from molecular biology. Finally, the appearance of the
genetic code in the late phase of the ribonucleopeptide world is discussed.
Received: 13 January 1997 / Accepted: 25 July 1997 相似文献
13.
Dr. Laura Curatolo Christine Chaponnier Maria Benedetta Donati Luciano Morasca Giulio Gabbiani 《Cell and tissue research》1982,223(3):665-673
Summary It is known that human and animal fibroblasts are able to induce the retraction of a fibrin clot. In the present study the correlation between (i) fibrinclot retractile (FCR) activity, (ii) the number of actin stress-lines in mouse fibroblasts during growth in culture, and (iii) the sensitivity of actin stress-lines to a powerful actin-depolymerizing factor (ADF), present in plasma and serum of humans and laboratory animals was investigated. Fibroblasts at early passages (2–4) were tested for these parameters at various intervals after seeding (24, 96, and 168 h). The number of actin stress-lines was progressively higher, while the sensitivity to ADF action was progressively lower in cells cultured from 24 to 168 h; the FCR capacity was significantly decreased at 168 h. These data suggest that cells containing weakly polymerized and/or stabilized actin are more active than those containing highly polymerized and/or stabilized actin in triggering fibroblast contraction. 相似文献
14.
Glutamate as a Putative Transmitter in the Cerebellum: Stimulation by GABA of Glutamic Acid Release from Specific Pools 总被引:8,自引:7,他引:1
The aim of the present paper was to determine whether the release of glutamate from putative "glutamergic" terminals in the cerebellum is influenced by gamma-aminobutyric acid (GABA). In a group of preliminary experiments, we present biochemical evidence in favour of a neurotransmitter role of glutamate in the cerebellum: (1) endogenous glutamate was released from depolarized cerebellar synaptosomal preparations in a Ca2+-dependent away; (2) [14C]glutamate was synthesized from [14C]glutamine in cerebellar synaptosomes, and the newly synthesized [14C]glutamate was released released in a Ca2+-dependent way; (3) the elevation of cyclic GMP elicited by depolarization of cerebellar slices in the presence of Ca2+ was partly reversed by the glutamate antagonist glutamic acid diethyl ester, which probably prevented the interaction of endogenously released glutamate with postsynaptic receptors. GABA and muscimol at low concentrations (2--20 micrometers) potentiated the depolarization-induced release of D-[3H]aspartate (a glutamate analogue which labels the glutamate "reuptake pool") from cerebellar synaptosomes. The effect was concentration dependent and was largely prevented by two GABA antagonists, bicuculline and picrotoxin. The stimulation of D-[3H]aspartate release evoked by muscimol was linearly related to the logarithm of K+ concentration in the depolarizing medium. GABA did not affect the overall release of endogenous glutamate, but potentiated, in a picrotoxin-sensitive manner, the depolarization-evoked release of [14C]glutamate previously synthesized from [14C]glutamine. Since nerve endings are the major site of glutamate synthesis from glutamine, GABA and muscimol appear to exert their stimulatory effect at the level of "glutamergic" nerve terminals, probably after interacting with presynaptic GABA receptors. The possible functional significance of these findings is briefly discussed. 相似文献
15.
Gerhard Toggenburger Max H?sermann Beat Mütsch Giulio Genoni Markus Kessler Fritz Weber Dietrich Hornig Brigitte ONeill Giorgio Semenza 《生物化学与生物物理学报:生物膜》1981,646(3):433-443
l-Ascorbate is taken up into brush border vesicles from kidney cortex of rat, rabbit and guinea pig by an efficient, Na+-dependent and potential-sensitive transport process. This uptake shows saturation () and is strongly stimulated by low concentrations of N3?. Erythorbate (d-isoascorbate) seems to be another, but poorer, substrate of the same transporter. 相似文献
16.
17.
Edward J. Leonard Alison Skeel Peter K. Chiang Giulio L. Cantoni 《Biochemical and biophysical research communications》1978,84(1):102-109
An inhibitor of adenosylhomocysteine hydrolase, 3-deazaadenosine, caused profound inhibition of phagocytosis of opsonized erythrocytes by mouse resident peritoneal macrophages . The inhibition was evident at concentrations as low as 2×10?7M, and increased with increasing concentration and time of exposure to the analogue. It was not associated with detachment of the macrophage monolayers or with loss of cell viability. Although the inhibition was not reversible, progression of the functional impairment was interrupted by washing out the analogue. In striking contrast, phagocytic function of human blood monocytes was unaffected by 3-deazaadenosine. 相似文献
18.
The effects of the ionophore A23187 and of ouabain on the release of [3H]GABA and [3H]norepinephrine were studied in superfused rat brain synaptosomes. Each of the two drugs moderately stimulated the spontaneous release of [3H]GABA, but greatly potentiated the release of [3H]GABA induced by unlabeled GABA. In contrast, the ionophore and norepinephrine showed an additive, but not a supraadditive, releasing effect on synaptosomal [3H]norepinephrine. Ouabain modestly and transiently potentiated the norepinephrine-induced [3H]norepinephrine release, which, however, was inhibited by the drug after a few minutes. It is suggested that in the new intrasynaptosomal ionic conditions determined by the two drugs, the stoichiometry of the basal homoexchange of GABA is changed in a direction favoring net outward transport. 相似文献
19.
Giulio Poli Ivana Barravecchia Gian Carlo Demontis Andrea Sodi Alessandro Saba Stanislao Rizzo Marco Macchia Tiziano Tuccinardi 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):1765
The human retinal pigment epithelium-specific 65-kDa protein (hRPE65) plays a crucial role within the retinoid visual cycle and several mutations affecting either its expression level or its enzymatic function are associated with inherited retinal diseases such as Retinitis Pigmentosa. The gene therapy product voretigene neparvovec (Luxturna) has been recently approved for treating hereditary retinal dystrophies; however, the treatment is currently accessible only to patients presenting confirmed biallelic mutations that severely impair hRPE65 function, and many reported hRPE65 missense mutations lack sufficient evidences for proving their pathogenicity. In this context, we developed a computational approach aimed at evaluating the potential pathogenic effect of hRPE65 missense variants located on the dimerisation domain of the protein. The protocol evaluates how mutations may affect folding and conformation stability of this protein region, potentially helping clinicians to evaluate the eligibility for gene therapy of patients diagnosed with this type of hRPE65 variant of uncertain significance. 相似文献
20.
Expression of adult fast pattern of acetylcholinesterase molecular forms by mouse satellite cells in culture 总被引:1,自引:0,他引:1
M. Immacolata Senni Francesco Castrignanò Giancarlo Poiana Giulio Cossu Gianfranco Scarsella Stefano Biagioni 《Differentiation; research in biological diversity》1987,36(3):194-198
The pattern of acetylcholinesterase (AChE) molecular forms, obtained by sucrose gradient sedimentation, was studied at different in vitro developmental stages of myogenic cells isolated from adult mouse skeletal muscle. Only the globular forms were present in rapidly dividing satellite cells during the first days in culture. After myotube formation, a pattern similar to that described in mammalian fast-twitch skeletal muscle was observed. This pattern did not change during the following period in culture (up to 1 month) nor could it be modified by co-culturing with spinal cord motoneurons or by addition of brain-derived extracts. The internal-external localization of AChE molecular forms has been determined by the use of echothiophate iodide, a membrane-impermeant irreversible inhibitor of AChE. Echothiophate-treated cultures showed about 40% of both asymmetric and globular forms localized on the sarcolemma, with their active sites oriented outward. Analysis of culture medium from untreated cultures revealed the presence of both asymmetric and globular forms. When the same analysis was repeated on cultures of myoblasts derived from 16-day-old mouse embryos, the pattern of AChE forms was different. The myotubes derived from these cells exhibit a very small proportion of asymmetric form, which was not released into the medium. This pattern was not further modified during the following days of culture, nor by co-cultures with spinal cord motoneurons or by incubations with brain-derived extracts. Thus, the myotubes derived from myoblasts express in culture a clear phenotypic difference when compared to the corresponding myotubes from satellite cells, supporting the view that these two myogenic cells are endowed with different developmental programs. 相似文献