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141.
Huffman JW Bushell SM Miller JR Wiley JL Martin BR 《Bioorganic & medicinal chemistry》2002,10(12):4119-4129
Three series of new cannabinoids were prepared and their affinities for the CB1 and CB2 cannabinoid recptors were determined. These are the 1-methoxy-3-(1′,1′-dimethylalkyl)-, 1-deoxy-11-hydroxy-3-(1′,1′-dimethylalkyl)- and 11-hydroxy-1-methoxy-3-(1′,1′-dimethylalkyl)-Δ8-tetrahydrocannabinols, which contain alkyl chains from dimethylethyl to dimethylheptyl appended to C-3 of the cannabinoid. All of these compounds have greater affinity for the CB2 receptor than for the CB1 receptor, however only 1-methoxy-3-(1′,1′-dimethylhexyl)-Δ8-THC (JWH-229, 6e) has effectively no affinity for the CB1 receptor (Ki=3134±110 nM) and high affinity for CB2 (Ki=18±2 nM). 相似文献
142.
Lai L Park KW Cheong HT Kühholzer B Samuel M Bonk A Im GS Rieke A Day BN Murphy CN Carter DB Prather RS 《Molecular reproduction and development》2002,62(3):300-306
Fetal-derived fibroblast cells were transduced with replication defective vectors containing the enhanced green fluorescent protein (EGFP). The transgenic cells were treated with colchicine, which theoretically would synchronize the cells into G2/M stage, and then used as donor nuclei for nuclear transfer. The donor cells were transferred into the perivitalline space of enucleated in vitro matured porcine oocytes, and fused and activated with electrical pulses. A total of 8.3% and 28.6% of reconstructed oocytes showed nuclear envelope breakdown and premature chromosome condensation 0.5 and 2 hr after activation, respectively. Percentage of pronuclear formation was 62.5, 12 hr after activation. Most (91.4%) of the 1-cell embryos with pronuclei did not extrude a polar body. Most (77.2%) embryos on day 5 were diploid. Within 2 hr after fusion, strong fluorescence was detectable in most reconstructed oocytes (92.3%). The fluorescence in all NT embryos became weak 15 hr after fusion and disappeared when culture to 48 hr. But from day 3, cleaved embryos at the 2- to 4-cell stage started to express EGFP again. On day 7, 85.8% of cleaved embryos expressed EGFP. A total of 9.4% of reconstructed embryos developed to blastocyst stage and 71.5% of the blastoctysts expressed EGFP. After 200 reconstructed 1-cell stage embryos were transferred into four surrogate gilts, three recipients were found to be pregnant. One of them maintained to term and delivered a healthy transgenic piglet expressing EGFP. Our data suggest that the combination of transduction of somatic cells by a replication defective vector with the nuclear transfer of colchicine-treated donors is an alternative to produce transgenic pigs. Furthermore, the tissues expressing EGFP from descendents of this pig may be very useful in future studies using pigs that require genetically marked cells. 相似文献
143.
Unfolded cholera toxin is transferred to the ER membrane and released from protein disulfide isomerase upon oxidation by Ero1
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The toxic effect of cholera toxin (CT) on target cells is caused by its A1 chain. This polypeptide is released from the holotoxin and unfolded in the lumen of the ER by the action of protein disulfide isomerase (PDI), before being retrotranslocated into the cytosol. The polypeptide is initially unfolded by binding to the reduced form of PDI. We show that upon oxidation of the COOH-terminal disulfide bond in PDI by the enzyme Ero1, the A1 chain is released. Both yeast Ero1 and the mammalian Ero1alpha isoform are active in this reaction. Ero1 has a preference for the PDI-toxin complex. We further show that the complex is transferred to a protein at the lumenal side of the ER membrane, where the unfolded toxin is released from PDI by the action of Ero1. Taken together, our results identify Ero1 as the enzyme mediating the release of unfolded CT from PDI and characterize an additional step in retrotranslocation of the toxin. 相似文献
144.
Human Dicer preferentially cleaves dsRNAs at their termini without a requirement for ATP 总被引:37,自引:0,他引:37
Dicer is a multi-domain RNase III-related endonuclease responsible for processing double-stranded RNA (dsRNA) to small interfering RNAs (siRNAs) during a process of RNA interference (RNAi). It also catalyses excision of the regulatory microRNAs from their precursors. In this work, we describe the purification and properties of a recombinant human Dicer. The protein cleaves dsRNAs into approximately 22 nucleotide siRNAs. Accumulation of processing intermediates of discrete sizes, and experiments performed with substrates containing modified ends, indicate that Dicer preferentially cleaves dsRNAs at their termini. Binding of the enzyme to the substrate can be uncoupled from the cleavage step by omitting Mg(2+) or performing the reaction at 4 degrees C. Activity of the recombinant Dicer, and of the endogenous protein present in mammalian cell extracts, is stimulated by limited proteolysis, and the proteolysed enzyme becomes active at 4 degrees C. Cleavage of dsRNA by purifed Dicer and the endogenous enzyme is ATP independent. Additional experiments suggest that if ATP participates in the Dicer reaction in mammalian cells, it might be involved in product release needed for the multiple turnover of the enzyme. 相似文献
145.
We demonstrate for the first time that ellipsometry and confocal fluorescence correlation spectroscopy (FCS) are complementary methods for the characterisation of supported planar phospholipid bilayers (SPBs) formed on mica, a mineral used in atomic force microscopy investigations of SPBs. Addition of small unilamellar vesicles containing 20% dioleoyl-phosphatidylserine (DOPS) and 80% dioleoyl-phosphatidylcholine (DOPC) to an oxidised borosilicate surface, on the other hand, results in a planar lipid system characterised by lateral diffusion coefficients which are three time smaller than those obtained for SPBs. Moreover, seven labelled phospholipids were tested for their suitability in the FCS characterisation of vesicles as well as of SPBs. 相似文献
146.
147.
Arginine in burn injury improves cardiac performance and prevents bacterial translocation 总被引:2,自引:0,他引:2
Horton Jureta W.; White Jean; Maass David; Sanders Billy 《Journal of applied physiology》1998,84(2):695-702
Horton, Jureta W., Jean White, David Maass, and BillySanders. Arginine in burn injury improves cardiac performance andprevents bacterial translocation. J. Appl.Physiol. 84(2): 695-702, 1998.This studyexamined the effects of arginine supplement of fluid resuscitation fromburn injury on cardiac contractile performance and bacterialtranslocation after a third-degree burn comprising 43% of the totalbody surface area in adult rats. Before burn injury, rats wereinstrumented to measure blood pressure; after burn (or sham injury),paired groups of sham-burned and burned rats were given vehicle(saline), L-arginine,D-arginine, orN-methyl-L-arginine(300 mg/kg in 0.3 ml of saline 30 min, 6 h, and 23 h postburn) plusfluid resuscitation; sham-burned rats received drug only.Twenty-four hours after burn trauma, hemodynamics were measured; theanimals were then killed and randomly assigned to Langendorff heartstudies or to studies examining translocation of gut bacteria. Burnrats treated with vehicle, D-arginine, orN-methyl-L-argininehad well-defined cardiocirculatory responses that included hypotension,tachycardia, respiratory compensation for metabolic acidosis,hypocalcemia, cardiac contractile depression, and significant bacterialtranslocation. Compared with values measured in vehicle-treated burnrats, L-arginine given afterburn improved blood pressure, prevented tachycardia, reduced serumlactate levels, improved cardiac performance, and significantly reducedbacterial translocation, confirming that L-arginine administration afterburn injury provided significant cardiac and gastrointestinalprotection. Circulating neutrophil counts fell after burn trauma andserum glucagon levels rose, but these changes were not altered bypharmacological intervention. Our finding of significantly highercoronary perfusate guanosine 3,5-cyclic monophosphateconcentration inL-arginine-treated burn ratssuggests that the beneficial effects ofL-arginine were mediated bynitric oxide production. 相似文献
148.
Billy W. Geer Stephen W. McKechnie Pieter W. H. Heinstra Manfred J. Pyka 《Evolution; international journal of organic evolution》1991,45(5):1107-1119
To help elucidate mechanisms of larval ethanol tolerance seven isochromosomal lines of Drosophila melanogaster with different second chromosomes were fed a growth-limiting concentration of ethanol (4.5% v/v) and examined for associations between growth traits and biochemical characteristics that had previously been implicated in the determination of tolerance variation. Repeated measures of survival and development time over four generations verified the inherited nature of these traits. Significant variation among the lines were evident for flux from ethanol into lipid, for activity levels of alcohol dehydrogenase and glycerol-3-phosphate oxidase (GPO), and for levels of long chain and unsaturated fatty acids. A high degree of positive association occurred among the variables. A partial correlation analysis controlling for performance of the lines on ethanol-free medium revealed a strong association between the degree of long chain fatty acid content and line survival when ethanol was fed. The correlation between GPO activity and survival in an ethanol environment appeared to depend on the association of GPO activity with long chain fatty acid content. The positive correlations of flux from ethanol into lipid with many of the other variables suggested that the ADH pathway influenced the level of ethanol tolerance. These associations are all consistent with the hypothesis that the lipid content of body tissues, especially the levels of long chain and unsaturated fatty acids in cell membranes, may have an important influence on both spatial and interspecific variation in the ethanol tolerance of larvae. 相似文献
149.
Billy B. Sellers Jr. Julia A. Hall Stanley A. Mendoza 《The Journal of membrane biology》1978,41(4):323-328
Summary The relationship between active Na transport (estimated by the short-circuit (SCC)) and active inorganic phosphate (Pi) transport was studied in the toad bladder. When SCC was inhibited by amiloride, ouabaim, or removal of K from the serosal bathing solution, active Pi transport was totally inhibited. When Na was replaced isotonically by choline in either the mucosal bathing solution or both the mucosal and serosal bathing solutions, there was no measurable SCC or active Pi transport. These experiments are compatible with the hypothesis that active Pi transport occurs only in the presence of active Na transport. 相似文献
150.
Dean Tsao Douglas G. Colton Judy S. Chang Robert L. Buck Billy G. Hudson Kermit L. Carraway 《生物化学与生物物理学报:生物膜》1977,469(1):61-73
Reticulocytosis was induced in rabbits by two methods: phlebotomy and injection of phenylhydrazine. Normal erythrocytes, reticulocytes from bed rabbits, reticulocytes from phenylhydrazine-treated rabbits, and erythrocytes treated in vitro with phenylhydrazine were compared with respect to their plasma membrane labeling by galactose oxidase and NaB3H4, and lactoperoxidase-catalyzed incorporation of 125I. Normal erythrocyte membranes and membranes from reticulocytes of bled rabbits showed almost identical labeling patterns, the presence of 2–3 glycoproteins with moderate to low mobilities on dodecyl sulfate acrylamide gel electrophoresis. Labeling in the absence of enzyme was negligible. In contrast, the reticulocytes from phenylhydrazine-treated rabbits exhibited a large incorporation of tritium without prior treatment with galactose oxidase. Even after prereduction with unlabeled NaBH4 to remove this nonspecific labeling, the labeled glycoprotein components found in normal erythrocytes were not detectable. Normal erythrocytes treated in vitro with phenylhydrazine, washed, and labeled with galactose oxidase had labeling patterns, including high nonspecific incorporation of 3H, similar to those observed with in vivo phenylhydrazine treatment.Solubilization of membranes with lithium diiososalicylate followed by partitioning with phenol showed that the same glycoproteins were presented in normal or phenylhydrazine membranes, although only the former extract was labeled by galactose oxidase. Individual carbohydrates from the membranes were analyzed by gas-liquid chromatography and, in the case of hexosamines, on the amino acid analyzer. The results of these analyses indicated a slight decline in galactose content with phenylhydrazine treatment. Reticulocyte membranes from bled rabbits also showed a decrease in galactose content, although it was less pronounced.Most of the label incorporated by nonspecific borohydride labeling of membranes from phenylhydrazine-treated animals was found associated with protein. The modified amino acids from labeled proteins are similar to those formed in reactions of oxidized lipids and proteins in model systems. 相似文献