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131.
Kim CS Davidoff AJ Maki TM Doye AA Gwathmey JK 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2000,170(4):295-306
Global contractile heart failure was induced in turkey poults by furazolidone feeding (700 ppm). Abnormal calcium regulation
appears to be a key factor in the pathophysiology of heart failure, but the cellular mechanisms contributing to changes in
calcium fluxes have not been clearly defined. Isolated ventricular myocytes from non-failing and failing hearts were therefore
used to determine whether the whole heart and ventricular muscle contractile dysfunctions were realized at the single cell
level. Whole cell current- and voltage-clamp techniques were used to evaluate action potential configurations and L-type calcium
currents, respectively. Intracellular calcium transients were evaluated in isolated myocytes with fura-2 and in isolated left
ventricular muscles using aequorin. Action potential durations were prolonged in failing myocytes, which correspond to slowed
cytosolic calcium clearing. Calcium current-voltage relationships were normal in failing myocytes; preliminary evidence suggests
that depressed transient outward potassium currents contribute to prolonged action potential durations. The number of calcium
channels (as measured by radioligand binding) were also similar in non-failing and failing hearts. Isolated ventricular muscles
from failing hearts had enhanced inotropic responses, in a dose-dependent fashion, to a calcium channel agonist (Bay K 8644).
These data suggest that changes in intracellular calcium mobilization kinetics and longer calcium-myofilament interaction
may be able to compensate for contractile failure. We conclude that the relationship between calcium current density and sarcoplasmic
reticulum calcium release is a dynamic process that may be altered in the setting of heart failure at higher contraction rates.
Accepted: 1 March 2000 相似文献
132.
Epidermal-type transglutaminase (TGase 3) is devoid of GTPase activity, but its TGase activity is inhibited by GTP as in the case of tissue-type TGase (TGase 2). In addition, the inhibition was not affected by the presence of higher concentrations of Ca ion. These results indicate that GTP interacts with TGase 3 in a manner different from its action on TGase 2. 相似文献
133.
To obtain a broad perspective of the events leading to spontaneous loss of heterozygosity (LOH), we have characterized the genetic alterations that functionally inactivated the URA3 marker hemizygously or heterozygously situated either on chromosome III or chromosome V in diploid Saccharomyces cerevisiae cells. Analysis of chromosome structure in a large number of LOH clones by pulsed-field gel electrophoresis and PCR showed that chromosome loss, allelic recombination, and chromosome aberration were the major classes of genetic alterations leading to LOH. The frequencies of chromosome loss and chromosome aberration were significantly affected when the marker was located in different chromosomes, suggesting that chromosome-specific elements may affect the processes that led to these alterations. Aberrant-sized chromosomes were detected readily in approximately 8% of LOH events when the URA3 marker was placed in chromosome III. Molecular mechanisms underlying the chromosome aberrations were further investigated by studying the fate of two other genetic markers on chromosome III. Chromosome aberration caused by intrachromosomal rearrangements was predominantly due to a deletion between the MAT and HMR loci that occurred at a frequency of 3.1 x 10(-6). Another type of chromosome aberration, which occurred at a frequency slightly higher than that of the intrachromosomal deletion, appeared to be caused by interchromosomal rearrangement, including unequal crossing over between homologous chromatids and translocation with another chromosome. 相似文献
134.
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136.
The copper transport protein Atox1 promotes neuronal survival 总被引:5,自引:0,他引:5
Kelner GS Lee M Clark ME Maciejewski D McGrath D Rabizadeh S Lyons T Bredesen D Jenner P Maki RA 《The Journal of biological chemistry》2000,275(1):580-584
Atox1, a copper transport protein, was recently identified as a copper-dependent suppressor of oxidative damage in yeast lacking superoxide dismutase. We have previously reported that Atox1 in the rat brain is primarily expressed in neurons, with the highest levels in distinct neuronal subtypes that are characterized by their high levels of metal, like copper, iron, and zinc. In this report, we have transfected the Atox1 gene into several neuronal cell lines to increase the endogenous level of Atox1 expression and have demonstrated that, under conditions of serum starvation and oxidative injury, the transfected neurons are significantly protected against this stress. This level of protection is comparable with the level of protection seen with copper/zinc superoxide dismutase and the anti-apoptotic gene bcl-2 that had been similarly transfected. Furthermore, neuronal cell lines transfected with a mutant Atox1 gene, where the copper binding domain has been modified to prevent metal binding, do not afford protection against serum starvation resulting in apoptosis. Therefore, Atox1 is a component of the cellular pathways used for protection against oxidative stress. 相似文献
137.
Complexes of four peptides [KWGK, KGWK, K(6MeW)GK, KG(6MeW)K] with the nucleic acids [poly(A), poly(C), poly(U), poly(I), and rG(8)] have been investigated by phosphorescence and optically detected magnetic resonance (ODMR) spectroscopy. The intrinsic spectroscopic probes used in these studies are tryptophan (W) and 6-methyltryptophan (6MeW). Binding to the nucleic acids results in a red-shift of the phosphorescence 0,0-band (delta E(0,0)) of the aromatic residue as well as a reduction of its zero-field splitting parameter (delta D). Results are compared with earlier studies of the HIV-1 nucleocapsid protein, NCp7, that contains a single tryptophan residue (Trp37) within a retroviral zinc finger sequence. Binding of poly(A) or poly(U) to the tetrapeptides induces larger delta E(0,0) and delta D than when bound to NCp7, indicating stronger stacking interactions. Poly(I), on the other hand, produces larger shifts in Trp37 of NCp7. Binding of rG(8) produces sequence-dependent effects in the peptides. When bound to NCp7, but in contrast with tetrapeptide binding, nucleic acids produce large changes in triplet state kinetics consistent with enhanced spin-orbit coupling. These results are discussed in terms of three limiting types of tryptophan-base interaction: intercalation, aromatic stacking, and edge-on interaction. These should have differing effects on the properties of the triplet state. 相似文献
138.
Structure and function of the fourth subunit (Dpb4p) of DNA polymerase epsilon in Saccharomyces cerevisiae
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DNA polymerase (Pol) of Saccharomyces cerevisiae is purified as a complex of four polypeptides with molecular masses of >250, 80, 34 (and 31) and 29 kDa as determined by SDS–PAGE. The genes POL2, DPB2 and DPB3, encoding the catalytic Pol2p, the second (Dpb2p) and the third largest subunits (Dpb3p) of the complex, respectively, were previously cloned and characterised. This paper reports the partial amino acid sequence of the fourth subunit (Dpb4p) of Pol. This protein sequence matches parts of the predicted amino acid sequence from the YDR121w open reading frame on S.cerevisiae chromosome IV. Thus, YDR121w was renamed DPB4. A deletion mutant of DPB4 (Δdpb4) is not lethal, but chromosomal DNA replication is slightly disturbed in this mutant. A double mutant haploid strain carrying the Δdpb4 deletion and either pol2-11 or dpb11-1 is lethal at all temperatures tested. Furthermore, the restrictive temperature of double mutants carrying Δdpb4 and dpb2-1, rad53-1 or rad53-21 is lower than in the corresponding single mutants. These results strongly suggest that Dpb4p plays an important role in maintaining the complex structure of Pol in S.cerevisiae, even if it is not essential for cell growth. Structural homologues of DPB4 are present in other eukaryotic genomes, suggesting that the complex structure of S.cerevisiae Pol is conserved in eukaryotes. 相似文献
139.
Amyloid protofilament formation of hen egg lysozyme in highly concentrated ethanol solution
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Goda S Takano K Yamagata Y Nagata R Akutsu H Maki S Namba K Yutani K 《Protein science : a publication of the Protein Society》2000,9(2):369-375
Mutant human lysozymes (Ile56Thr & Asp67His) have been reported to form amyloid deposits in the viscera. From the standpoint of understanding the mechanism of amyloid formation, we searched for conditions of amyloid formation in vitro using hen egg lysozyme, which has been extensively studied from a physicochemical standpoint. It was found that the circular dichroism spectra in the far-ultraviolet region of the hen egg lysozyme changed to those characteristic of a beta-structure from the native alpha-helix rich spectrum in 90% ethanol solution. When the concentration of protein was increased to 10 mg/mL, the protein solution formed a gel in the presence of 90% ethanol, and precipitated on further addition of 10 mM NaCl. The precipitates were examined by electron microscopy, their ability to bind Congo red, and X-ray diffraction to determine whether amyloid fibrils were formed in the precipitates. Electron micrographs displayed unbranched protofilament with a diameter of approximately 70 A. The peak point of the difference spectrum for the Congo red binding assay was 541 nm, which is characteristic of amyloid fibrils. The X-ray diffraction pattern showed a sharp and intense diffraction ring at 4.7 A, a reflection that arises from the interstrand spacing in beta-sheets. These results indicate that the precipitates of hen egg lysozyme are amyloid protofilament, and that the amyloid protofilament formation of hen egg lysozyme closely follows upon the destruction of the helical and tertiary structures. 相似文献
140.
A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains 总被引:26,自引:0,他引:26
Peyron C Faraco J Rogers W Ripley B Overeem S Charnay Y Nevsimalova S Aldrich M Reynolds D Albin R Li R Hungs M Pedrazzoli M Padigaru M Kucherlapati M Fan J Maki R Lammers GJ Bouras C Kucherlapati R Nishino S Mignot E 《Nature medicine》2000,6(9):991-997
We explored the role of hypocretins in human narcolepsy through histopathology of six narcolepsy brains and mutation screening of Hcrt, Hcrtr1 and Hcrtr2 in 74 patients of various human leukocyte antigen and family history status. One Hcrt mutation, impairing peptide trafficking and processing, was found in a single case with early onset narcolepsy. In situ hybridization of the perifornical area and peptide radioimmunoassays indicated global loss of hypocretins, without gliosis or signs of inflammation in all human cases examined. Although hypocretin loci do not contribute significantly to genetic predisposition, most cases of human narcolepsy are associated with a deficient hypocretin system. 相似文献