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41.
Sílvia Bronsoms Josep Villanueva Francesc Canals Enrique Querol Francesc X Aviles 《European journal of biochemistry》2003,270(17):3641-3650
Protein folding can be modulated in vivo by many factors. While chaperones act as folding catalysts and show broad substrate specificity, some pro-peptides specifically facilitate the folding of the mature protein to which they are bound. Potato carboxypeptidase inhibitor (PCI), a 39-residue protein carboxypeptidase inhibitor, is synthesized in vivo as a precursor protein that includes a 27-residue N-terminal and a seven-residue C-terminal pro-regions. In this work the disulfide-coupled folding of mature PCI in vitro has been compared with that of the same protein extended with either the N-terminal pro-sequence (ProNtPCI) or both N- and C-terminal pro-sequences (ProPCI), and also with the N-terminal pro-sequence in trans (ProNt + PCI). No significant differences can be observed in the folding kinetics or efficiencies of all these molecules. In addition, in vivo folding studies in Escherichia coli have been performed using wild-type PCI and three PCI mutant forms with and without the N-terminal pro-sequence, the mutations had been previously reported to affect folding of the PCI mature form. The extent to which the 'native-like' form was secreted to the media by each construction was not affected by the presence of the N-terminal pro-sequence. These results indicate that PCI does not depend on the N-terminal pro-sequence for its folding in both, in vitro and in vivo in E. coli. However, structural analysis by spectroscopy, hydrogen exchange and limited proteolysis by mass spectrometry, indicate the capability of such N-terminal pro-sequence to fold within the precursor form. 相似文献
42.
Michael J. Seckl Richard H. Newman Paul S. Freemont Enrique Rozengurt 《Journal of cellular physiology》1995,163(1):87-95
The substance P (SP) analogues [DArg1, DPhe5, DTrp7,9, Leu11] SP (AntD) and [Arg6, DTrp7,9, MePhe8] SP (6–11) (AntG) inhibit the action of many different neuropeptides including SP. These analogues might be useful in the treatment of small cell lung cancer but their mechanism of action is unclear. Here, we analyzed the effect of AntD and AntG on neuropeptide vs. guanosine 5′-3-O-(thio) triphosphate (GTPγS) stimulated inositol phosphate generation in permeabilized Swiss 3T3 cells. AntD inhibited vasopressin and bombesin stimulated inositol phosphate formation (IC50 of 0.75 μM and 2 μM, respectively). Similarly, AntG inhibited vasopressin-stimulated inositol phosphate generation with an IC50 of 1 μM. Strikingly, neither AntD up to 10 μM nor AntG up to 20 μM was able to inhibit GTPγS-stimulated inositol phosphate generation. Dose-response curves of neuropeptide-induced inositol phosphate generation were dramatically displaced to the right by either 10 μM AntD or 20 μM AntG. However, neither antagonist affected the dose response of GTPγS-stimulated inositol phosphate generation. Furthermore, 20 μM AntD had no effect on AIF?4-induced inositol phosphates in COS-1 cells transfected with Gαq. AntD inhibited [3H]vasopressin binding competitively in intact Swiss 3T3 cells and both AntD and AntG inhibited [3H]vasopressin binding in Swiss 3T3 and rat liver membranes. Scatchard analysis revealed that AntD inhibited vasopressin binding by reducing receptor affinity without affecting receptor number in both intact and membrane preparations of Swiss 3T3 cells. The results strongly suggest that SP analogues AntD and AntG block the action of the Ca2+ mobilizing neuropeptides at the receptor level, rather than inhibiting G protein-stimulated inositol phosphate production. © 1995 Wiley-Liss, Inc. 相似文献
43.
Abstract: Different neurotransmitter receptor agonists [carbachol, serotonin, noradrenaline, histamine, endothelin-1, and trans -(1 S ,3 R )-aminocyclopentyl-1,3-dicarboxylic acid ( trans -ACPD)], known as stimuli of phospholipase C in brain tissue, were tested for phospholipase D stimulation in [32 P]Pi -prelabeled rat brain cortical and hippocampal slices. The accumulation of [32 P]phosphatidylethanol was measured as an index of phospholipase D-catalyzed transphosphatidylation in the presence of ethanol. Among the six neurotransmitter receptor agonists tested, only noradrenaline, histamine, endothelin-1, and trans -ACPD stimulated phospholipase D in hippocampus and cortex, an effect that was strictly dependent of the presence of millimolar extracellular calcium concentrations. The effect of histamine (EC50 18 µ M ) was inhibited by the H1 receptor antagonist mepyramine with a K i constant of 0.7 n M and was resistant to H2 and H3 receptor antagonists (ranitidine and tioperamide, respectively). Endothelin-1-stimulated phospholipase D (EC50 44 n M ) was not blocked by BQ-123, a specific antagonist of the ETA receptor. Endothelin-3 and the specific ETB receptor agonist safarotoxin 6c were also able to stimulate phospholipase D with efficacies similar to that of endothelin-1, and EC50 values of 16 and 3 n M , respectively. These results show that histamine and endothelin-1 stimulate phospholipase D in rat brain through H1 and ETB receptors, respectively. 相似文献
44.
Jesús Mateo Enrique Castro Jean Zwiller Dominique Aunis M. T. Miras-Portugal 《Journal of neurochemistry》1995,64(1):77-84
Abstract: We investigated the effect of the adenosine receptor agonist 5'-( N -ethylcarboxamido)adenosine (NECA) in catecholamine secretion from adrenal chromaffin cells that exhibit only the A2b subtype adenosine receptor. NECA reduced catecholamine release evoked by the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP) in a time-dependent manner. Inhibition reached 25% after 30–40-min exposure to NECA. This effect on DMPP-evoked catecholamine secretion was mirrored by a similar (27.7 ± 3.3%), slowly developing inhibition of [Ca2+ ]i transients induced by DMPP that peaked at 30-min preincubation with NECA. The capacity of the chromaffin cells to buffer Ca2+ load was not affected by the treatment with NECA. Short-term treatment with NECA failed both to modify [Ca2+ ]i levels and to increase endogenous diacylglycerol production, showing that NECA does not activate the intracellular Ca2+ /protein kinase C signaling pathway. The inhibitory effects of NECA were accompanied by a 30% increase of protein phosphatase activity in chromaffin cell cytosol. We suggest that dephosphorylation of a protein involved in DMPP-evoked Ca2+ influx pathway (e.g., L-type Ca2+ channels) could be the mechanism of the inhibitory action of adenosine receptor stimulation on catecholamine secretion from adrenal chromaffin cells. 相似文献
45.
Ruth Meléndez Enrique Meléndez-Hevia Marta Cascante 《Journal of molecular evolution》1997,45(4):446-455
Optimization of molecular design in cellular metabolism is a necessary condition for guaranteeing a good structure–function
relationship. We have studied this feature in the design of glycogen by means of the mathematical model previously presented
that describes glycogen structure and its optimization function [Meléndez-Hevia et al. (1993), Biochem J 295: 477–483]. Our
results demonstrate that the structure of cellular glycogen is in good agreement with these principles. Because the stored
glucose in glycogen must be ready to be used at any phase of its synthesis or degradation, the full optimization of glycogen
structure must also imply the optimization of every intermediate stage in its formation. This case can be viewed as a molecular
instance of the eye problem, a classical paradigm of natural selection which states that every step in the evolutionary formation of a functional structure
must be functional. The glycogen molecule has a highly optimized structure for its metabolic function, but the optimization
of the full molecule has meaning and can be understood only by taking into account the optimization of each intermediate stage
in its formation.
Received: 23 October 1996 / Accepted: 21 April 1997 相似文献
46.
Enrique A. Gonzlez Froiln Vzquez Jos Ignacio Garabal Jorge Blanco 《Microbiology and immunology》1995,39(12):937-942
Fimbriae isolation by means of thermal shock was applied to fifteen K88-positive (three K88ab, nine K88ac and three K88ad) Escherichia coli reference strains belonging to serotypes O8:K87, O32, O45, O138:K81, O141:K85, O147:K89, O149:K91, and O157, as well as to ten K88-positive enterotoxigenic strains isolated from porcine diarrhea in Spain, all of them belonging to the O149 serogroup. Fimbriae were removed from the bacterial cells by thermal shock at 60 C and then precipitated using ammonium sulfate. The final amount of K88 antigen and the purification degree were not related to the serogroup of the bacteria or to the antigen variant but were related to the buffer used for isolation. Phosphate buffer containing urea was shown to be more effective than Tris-HCl for isolation of K88 antigen. The molecular weights by SDS-PAGE for K88ab, K88ac, and K88ad were 28.5, 29.2, and 31.0 kDa, respectively. All enterotoxigenic E. coli strains isolated in Spain showed the K88ac variant. 相似文献
47.
48.
Ernesto Bonilla Enrique Salazar Jose Joaquin Villasmil Ruddy Villalobos Magaly Gonzalez Jose Omar Davila 《Neurochemical research》1984,9(11):1543-1548
Copper concentration was determined in samples from 38 areas of 7 normal human brains. The grey matter contained higher concentrations of copper than the white matter. Identical areas of the grey and white matter of the cerebral cortex showed significant differences between individuals. In the caudate nucleus the highest concentrations of copper were found in the tail followed by the body and the head, respectively. A negative linear regression between age and brain copper levels was demonstrated. 相似文献
49.
Temporal integration of pungency 总被引:9,自引:4,他引:5
Four experiments explored possible temporal summation in olfactionand the common chemical sense. In one experiment, participantsjudged the perceived magnitude of various concentrations anddurations (1.253.75 s) of the pungent odorant ammoniaand the nonpungent odorant isoamyl butyrate. The perceived magnitudeof ammonia increased during an inhalation whereas the magnitudeof isoamyl butyrate did not. Time-intensity trading relationsfor ammonia indicated nearly perfect temporal summation. Inanother experiment, modulation of the concentration of ammoniaduring an inhalation led to assessments of perceived magnitudethat confirmed the high degree of temporal summation seen inthe first experiment. That is, approximately equal time-integratedmass of inhaled ammonia led to approximately equal perceivedintensity. A third experiment indicated that temporal summationfor ammonia arose from its pungency rather than from its odor,a fourth that trigeminally-mediated reflex apnea in responseto ammonia also exhibits temporal summation. The degree of temporalsummation measured with the reflex came very close to that assessedpsychophysically. When stimulated with ammonia, the common chemicalsense behaves more like a totalmass detector than a concentrationdetector. The investigation raises the possibility that theshortterm sensory reaction to most pungent stimuli may followthis simple rule. 相似文献
50.
The stimulation of poly(U)-directed polyphenylalanine synthesis produced by modification ofEscherichia coli ribosomes withp-hydroxymercuribenzoate, at low molar ratios of reagent to ribosomes, is due to an increase in the average chain length of polyphenylalanine synthesized, and not to the activation of inactive ribosomes. At a higher molar ratio ofp-hydroxymercuribenzoate to ribosomes, which produces no overall change in activity, approximately 50% of the active ribosomes present in the untreated preparation have been completely inactivated, and the remaining active ones, like the ribosomes of the stimulated preparation, synthesize polyphenylalanine at an increased rate as compared with the untreated ribosomes.Abbreviations pHMB
p-hydroxymercuribenzoate
- SucNBr
N-bromosuccinimide 相似文献