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991.
Serù R Mondola P Damiano S Svegliati S Agnese S Avvedimento EV Santillo M 《Journal of neurochemistry》2004,91(3):613-622
In this study we have investigated the effects of the small GTP-binding-protein Ras on the redox signalling of the human neuroblastoma cell line, SK-N-BE stably transfected with HaRas(Val12). The levels of reactive oxygen species (ROS) and superoxide anions were significantly higher in HaRas(Val12) expressing (SK-HaRas) cells than in control cells. The treatment of cells with 4-(2-aminoethyl) benzenesulfonylfluoride, a specific inhibitor of the membrane superoxide generating system NADPH oxidase, suppressed the rise in ROS and significantly reduced superoxide levels produced by SK-HaRas cells. Moreover, HaRas(Val12) induced the translocation of the cytosolic components of the NADPH oxidase complex p67(phox) and Rac to the plasma membrane. These effects depended on the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK1/2) pathway, as the specific MEK inhibitor, PD98059, prevented HaRas-mediated increase in ROS and superoxide anions. In contrast, the specific phosphoinositide 3-kinase (PI3K) inhibitors LY294002 and wortmannin were unable to reverse the effects of HaRas(Val12). Moreover, cholinergic stimulation of neuroblastoma cells by carbachol, which activated endogenous Ras/ERK1/2, induced a significant increase in ROS levels and elicited membrane translocation of p67(phox) and Rac. ROS generation induced by carbachol required the activation of ERK1/2 and PI3K. Hence, these data indicate that HaRas-induced ERK1/2 signalling selectively activates NADPH oxidase system in neuroblastoma cells. 相似文献
992.
993.
Prioni S Mauri L Loberto N Casellato R Chigorno V Karagogeos D Prinetti A Sonnino S 《Glycoconjugate journal》2004,21(8-9):461-470
Interactions between gangliosides and proteins at the exoplasmic surface of the sphingolipid-enriched membrane domains can be studied by ganglioside photolabeling combined with cell surface biotin labeling. In the present paper, we report on the results obtained using a novel radioactive photoactivable derivative of GM1 ganglioside, carrying the photoactivable nitrophenylazide group at the external galactose.After cell photolabeling with the radioactive photoactivable derivative of GM1 and cell surface biotin labeling, sphingolipid-enriched domains were prepared from rat cerebellar neurons differentiated in culture and further purified by immunoprecipitation with streptavidin-coupled beads. Among proteins belonging to the sphingolipid-enriched domains that were biotin labeled, thus bearing an exoplasmic domain, a few were also cross-linked by the radioactive photoactivable ganglioside. In particular, two protein bands showing apparent molecular mass of 135 and 35 kDa were intensely photolabeled. The 135 kDa protein was immunologically identified as the GPI-anchored neural cell adhesion molecule TAG-1. These data suggest that hydrophilic interaction between the exoplasmic domains of the protein and the ganglioside sialooligosaccharide chain could exist. Published in 2004. 相似文献
994.
The procedures for the preparation of radioactive and photoactivable ganglioside derivatives have been continuously developed from 1989, when for the first time the synthesis of photoactivable tritium labeled GM1 ganglioside was presented. We described previously the synthesis of photoactivable derivatives of GM3 and GM1 gangliosides, tritium-labeled at acetyl group of sugar units, and of photoactivable GM1 and GD1b gangliosides, tritium-labeled at position 6 of the external galactose. These procedures are reviewed in detail in the present paper.The use of these ganglioside derivatives to study the ganglioside-protein interactions and to identify proteins that specifically interact with gangliosides (including GPI-anchored proteins of the outer membrane leaflet, proteins anchored to the cytoplasmic side of the plasma membrane through a fatty acyl chain, transmembrane proteins, and soluble cytoplasmic proteins) is discussed. 相似文献
995.
996.
Russo A Corsale S Cammareri P Agnese V Cascio S Di Fede G Macaluso M Bazan V 《Journal of cellular physiology》2005,204(3):742-749
The recent introduction of new drugs such as capecitabine, irinotecan, and oxaliplatinum has greatly improved the clinical outcome of patients with advanced/metastatic colorectal cancer. Nevertheless, some patients may suffer from the adverse drug reactions which will probably be the main cause of chemotherapy failure. The goal of pharmacogenomics is to find correlations between therapeutic responses to drugs and the genetic profiles of patients; the different responses to a particular drug are due, in fact, not only to the specific clinico-pathological features of the patient or to environmental factors, but also to the ethnic origins and the particular individual's genetic profile. Genes which codify for the metabolism enzymes, receptor proteins, or protein targets of chemotherapy agents often present various genetic polymorphisms. The main aim of this review is to provide an overview of the known polymorphisms present in the genes which codify for factors (thymidylate synthase dihydropyrimidine dehydrogenase, uridine diphosphate (UDP)-glucuronosyl-transferase 1A1, enzymes implicated in DNA repair) involved in the action mechanisms of the drugs now utilized in chemotherapeutic treatment of colorectal carcinoma, such as fluoropyrimidines, irinotecan, and platinum agents. 相似文献
997.
998.
Steif PS Palastro M Wan CR Baicu S Taylor MJ Rabin Y 《Cell preservation technology》2005,3(3):184-200
A new imaging device, termed a "cryomacroscope", was used to observe macrofractures in the cryoprotectant cocktails DP6 and VS55. Details of the design and construction of the cryomacroscope were presented in Part I of this report, which focused on describing the apparatus and observations of crystallization. Part I and the current paper (Part II) describe events that occur as 1 m? of cryoprotectant contained in a glass vial is cooled from room temperature down to cryogenic temperatures (~ -135°C). The presence of cracking, as well as patterns in their position and orientation, are found to be dependent on the cooling rate and on the specific cryoprotectant cocktail. Cracks, if present, disappear upon rewarming, although they appear to be sites for later preferential crystallization. Computations which predict temperatures and mechanical stresses are used to explain observations of cracking. In conjunction with these reports, additional photos of cryomacroscopy of vitrification, crystallization, and fracture formation are available at http://www.me.cmu.edu/faculty1/rabin/CryomacroscopyImages01.htm. 相似文献
999.
Jure Borišek Sara Pintar Mitja Ogrizek Simona Golič Grdadolnik Vesna Hodnik Dušan Turk 《Journal of enzyme inhibition and medicinal chemistry》2018,33(1):1239-1247
Autolysin E (AtlE) is a cell wall degrading enzyme that catalyzes the hydrolysis of the β-1,4-glycosidic bond between the N-acetylglucosamine and N-acetylmuramic acid units of the bacterial peptidoglycan. Using our recently determined crystal structure of AtlE from Staphylococcus aureus and a combination of pharmacophore modeling, similarity search, and molecular docking, a series of (Phenylureido)piperidinyl benzamides were identified as potential binders and surface plasmon resonance (SPR) and saturation-transfer difference (STD) NMR experiments revealed that discovered compounds bind to AtlE in a lower micromolar range. (phenylureido)piperidinyl benzamides are the first reported non-substrate-like compounds that interact with this enzyme and enable further study of the interaction of small molecules with bacterial AtlE as potential inhibitors of this target. 相似文献