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101.
102.
Jos Francisco Qulez del Moral lvaro Prez Alejandro F. Barrero 《Phytochemistry Reviews》2020,19(3):559-576
Many terpenoids are biosynthesized after a cascade of cyclizations and rearrangements of carbocations mediated by terpenoid synthases, as exemplified in th 相似文献
103.
Intramembrane Charge Movement Associated with Endogenous K+ Channel Activity in HEK-293 Cells 总被引:1,自引:0,他引:1
1. The use of molecular biology in combination with electrophysiology in the HEK-293 cell line has given fascinating insights into neuronal ion channel function. Nevertheless, to fully understand the properties of channels exogenously expressed in these cells, a detailed evaluation of endogenous channels is indispensable. 2. Previous studies have shown the expression of endogenous voltage-gated K+, Ca2+, and Cl- channels and this predicts that changes in membrane potential will cause intramembrane charge movement, though this gating charge translocation remain undefined. Here, we confirm this prediction by performing patch-clamp experiments to record ionic and gating currents. Our data show that HEK-293 cells express at least two types of K+-selective endogenous channels which sustain the majority of the ionic current, and exclude a significant contribution from Ca2+ and Cl- channels to the whole-cell current. 3. Gating currents were unambiguously resolved after ionic current blockade enabling this first report of intramembrane charge movement in HEK-293 cells arising entirely from endogenous K+ channel activity, and providing valuable information concerning the activation mechanism of voltage-gated K+ channels in these cells. 相似文献
104.
López-Hernández GY Biaggi-Labiosa NM Torres-Cintrón A Ortiz-Acevedo A Lasalde-Dominicci JA 《Cellular and molecular neurobiology》2009,29(1):41-53
Phosphorylation of the nicotinic acetylcholine receptor (nAChR) is believed to play a critical role in its nicotine-induced
desensitization and up-regulation. We examined the contribution of a consensus PKC site in the α4 M3/M4 intracellular loop
(α4S336) on the desensitization and up-regulation of α4β2 nAChRs expressed in oocytes. Position α4S336 was replaced with either
alanine to abolish potential phosphorylation at this site or with aspartic acid to mimic phosphorylation at this same site.
Mutations α4S336A and α4S336D displayed a threefold increase in the ACh-induced response and an increase in ACh EC50. Epibatidine binding revealed a three and sevenfold increase in surface expression for the α4S336A and α4S336D mutations,
respectively, relative to wild-type, therefore, both mutations enhanced expression of the α4β2 nAChR. Interestingly, the EC50’s and peak currents for nicotine activation remained unaffected in both mutants. Both mutations abolished the nicotine-induced
up-regulation that is normally observed in the wild-type. The present data suggest that adding or removing a negative charge
at this phosphorylation site cannot be explained by a simple straightforward on-and-off mechanism; rather a more complex mechanism(s)
may govern the functional expression of the α4β2 nAChR. Along the same line, our data support the idea that phosphorylation
at multiple consensus sites in the α4 subunit could play a remarkable role on the regulation of the functional expression
of the α4β2 nAChR. 相似文献
105.
Alejandro G. Farji-Brener Ernesto Gianoli Marco A. Molina-Montenegro 《Ecological Research》2009,24(1):139-145
Small-scale disturbances caused by animals often modify soil resource availability and may also affect plant attributes. Changes
in the phenotype of plants growing on disturbed, nutrient-enriched microsites may influence the distribution and abundance
of associated insects. We evaluated how the high nutrient availability generated by leaf-cutting ant nests in a Patagonian
desert steppe may spread along the trophic chain, affecting the phenotype of two thistle species, the abundance of a specialist
aphid and the composition of the associated assemblage of tending ants. Plants of the thistle species Carduus nutans and Onopordum acanthium growing in piles of waste material generated by leaf-cutting ant nests (i.e., refuse dumps) had more leaves, inflorescences
and higher foliar nitrogen content than those in non-nest soils. Overall, plants in refuse dumps showed higher abundance of
aphids than plants in non-nest soils, and aphid colonies were of greater size on O. acanthium plants than on C. nutans plants. However, only C. nutans plants showed an increase in aphid abundance when growing on refuse dumps. This resulted in a similar aphid load in both
thistle species when growing on refuse dumps. Accordingly, only C. nutans showed an increase in the number of ant species attending aphids when growing on refuse dumps. The increase of soil fertility
generated by leaf-cutting ant nests can affect aphid abundance and their tending ant assemblage through its effect on plant
size and quality. However, the propagation of small-scale soil disturbances through the trophic chain may depend on the identity
of the species involved. 相似文献
106.
Alejandro P. Pariani Evangelina Almada Florencia Hidalgo Carla Borini-Etichetti Rodrigo Vena Leandra Marín Cristián Favre James R. Goldenring Maria Cecilia Larocca 《Journal of cellular physiology》2023,238(1):227-241
The elimination of transformed and viral infected cells by natural killer (NK) cells requires a specialized junction between NK and target cells, denominated immunological synapse (IS). After initial recognition, the IS enables the directed secretion of lytic granules content into the susceptible target cell. The lymphocyte function-associated antigen (LFA)-1 regulates NK effector function by enabling NK-IS assembly and maturation. The pathways underlying LFA-1 accumulation at the IS in NK cells remained uncharacterized. A kinase anchoring protein 350 (AKAP350) is a centrosome/Golgi-associated protein, which, in T cells, participates in LFA-1 activation by mechanisms that have not been elucidated. We first evaluated AKAP350 participation in NK cytolytic activity. Our results showed that the decrease in AKAP350 levels by RNA interference (AKAP350KD) inhibited NK-YTS cytolytic activity, without affecting conjugate formation. The impairment of NK effector function in AKAP350KD cells correlated with decreased LFA-1 clustering and defective IS maturation. AKAP350KD cells that were exclusively activated via LFA-1 showed impaired LFA-1 organization and deficient lytic granule translocation as well. In NK AKAP350KD cells, activation signaling through Vav1 was preserved up to 10 min of interaction with target cells, but significantly decreased afterwards. Experiments in YTS and in ex vivo NK cells identified an intracellular pool of LFA-1, which partially associated with the Golgi apparatus and, upon NK activation, redistributed to the IS in an AKAP350-dependent manner. The analysis of Golgi organization indicated that the decrease in AKAP350 expression led to the disruption of the Golgi integrity in NK cells. Alteration of Golgi function by BFA treatment or AKAP350 delocalization from this organelle also led to impaired LFA-1 localization at the IS. Therefore, this study characterizes AKAP350 participation in the modulation of NK effector function, revealing the existence of a Golgi-dependent trafficking pathway for LFA-1, which is relevant for LFA-1 organization at NK-lytic IS. 相似文献
107.
Lopez-Herrera G Tampella G Pan-Hammarström Q Herholz P Trujillo-Vargas CM Phadwal K Simon AK Moutschen M Etzioni A Mory A Srugo I Melamed D Hultenby K Liu C Baronio M Vitali M Philippet P Dideberg V Aghamohammadi A Rezaei N Enright V Du L Salzer U Eibel H Pfeifer D Veelken H Stauss H Lougaris V Plebani A Gertz EM Schäffer AA Hammarström L Grimbacher B 《American journal of human genetics》2012,90(6):986-1001
Most autosomal genetic causes of childhood-onset hypogammaglobulinemia are currently not well understood. Most affected individuals are simplex cases, but both autosomal-dominant and autosomal-recessive inheritance have been described. We performed genetic linkage analysis in consanguineous families affected by hypogammaglobulinemia. Four consanguineous families with childhood-onset humoral immune deficiency and features of autoimmunity shared genotype evidence for a linkage interval on chromosome 4q. Sequencing of positional candidate genes revealed that in each family, affected individuals had a distinct homozygous mutation in LRBA (lipopolysaccharide responsive beige-like anchor protein). All LRBA mutations segregated with the disease because homozygous individuals showed hypogammaglobulinemia and autoimmunity, whereas heterozygous individuals were healthy. These mutations were absent in healthy controls. Individuals with homozygous LRBA mutations had no LRBA, had disturbed B cell development, defective in vitro B cell activation, plasmablast formation, and immunoglobulin secretion, and had low proliferative responses. We conclude that mutations in LRBA cause an immune deficiency characterized by defects in B cell activation and autophagy and by susceptibility to apoptosis, all of which are associated with a clinical phenotype of hypogammaglobulinemia and autoimmunity. 相似文献
108.
109.
Mutations in the human homolog of the Vhlh gene [encoding the von-Hippel Lindau (VHL) protein] lead to tumor development. In mice, depletion of Vhlh in pancreatic ß-cells causes perturbed glucose homeostasis, but the role of this gene in other pancreatic cells is poorly understood. To investigate the function of VHL/HIF pathway in pancreatic cells, we inactivated Vhlh in the pancreatic epithelium as well as in the endocrine and exocrine lineages. Our results show that embryonic depletion of Vhlh within the pancreatic epithelium causes postnatal lethality due to severe hypoglycemia. The hypoglycemia is recapitulated in mice with endocrine-specific removal of Vhlh, while animals with loss of Vhlh predominantly in the exocrine compartment survive to adulthood with no overt defects in glucose metabolism. Mice with hypoglycemia display diminished insulin release in response to elevated glucose. Significantly, the glucagon response is impaired both in vivo (circulating glucagon levels) as well as in an in vitro secretion assay in isolated islets. Hypoxia also impairs glucagon secretion in a glucagon-expressing cell line in culture. Our results reveal a novel role for the hypoxia/HIF pathway in islet hormone secretion and maintenance of the fine balance that allows for the establishment of normoglycemia. 相似文献
110.