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101.
L. H. Brent B. Rubenstein Q. H. Gong S. J. Wieland 《Journal of cellular physiology》1996,168(1):155-165
Myeloid cells, including granulocytes and monocyte/macrophages, are important in disease-associated inflammatory reactions. These cells come from a common progenitor, the promyelocyte. The human promyelocytic cell line, HL-60, can be induced to terminally differentiate into granulocytes or monocyte/macrophages in a controlled fashion providing a model to study various aspects of myelomonocytic differentiation. The expression of several ion channels is controlled in HL-60 cells in a differentiation specific pattern. The purpose of this study was to determine if lineage-specific ion channel expression during HL-60 differentiation resulted in differences in functional responses to external stimuli. This was investigated by examining transmembrane potential responses in HL-60 promyelocytes, HL-60-derived polymorphonuclear cells (PMNs), and monocytes to various stimuli using the transmembrane potential sensitive dye, diSBAC2-(3). Exposure of HL-60 promyelocytes to ionomycin or ATP produced a membrane hyperpolarization. Studies using ion substitutions and ion channel blockers indicate that the hyperpolarization was mediated by KCa channels. During HL-60 promyelocyte differentiation to PMNs, the membrane potential response to ionomycin and ATP shifted from a hyperpolarization to a depolarization over 7 days. Conversely, HL-60-derived monocytes exhibited a membrane hyperpolarization in response to ionomycin and ATP. HL-60-derived monocytes also exhibit a Cl− conductance specifically induced by ATP. Lineage-specific expression of ion channels during HL-60 cell differentiation is important in determining the transmembrane potential response of these cells. This may be translated into functional responses of various myelomonocytic cells during disease-associated inflammatory reactions. © 1996 Wiley-Liss, Inc. 相似文献
102.
Kristina H. Schmidt Emilie Viebranz Lillian Doerfler Christina Lester Aaron Rubenstein 《PloS one》2010,5(8)
Genome instability, associated with chromosome breakage syndromes and most human
cancers, is still poorly understood. In the yeast Saccharomyces
cerevisiae, numerous genes with roles in the preservation of genome
integrity have been identified. DNA-damage-checkpoint-deficient yeast cells that
lack Sgs1, a RecQ-like DNA helicase related to the human
Bloom''s-syndrome-associated helicase BLM, show an increased rate of
genome instability, and we have previously shown that they accumulate recurring
chromosomal translocations between three similar genes, CAN1,
LYP1 and ALP1. Here, the chromosomal
location, copy number and sequence similarity of the translocation targets
ALP1 and LYP1 were altered to gain insight
into the formation of complex translocations. Among 844 clones with chromosomal
rearrangements, 93 with various types of simple and complex translocations
involving CAN1, LYP1 and ALP1
were identified. Breakpoint sequencing and mapping showed that the formation of
complex translocation types is strictly dependent on the location of the
initiating DNA break and revealed that complex translocations arise via a
combination of interchromosomal translocation and template-switching, as well as
from unstable dicentric intermediates. Template-switching occurred between
sequences on the same chromosome, but was inhibited if the genes were
transferred to different chromosomes. Unstable dicentric translocations
continuously gave rise to clones with multiple translocations in various
combinations, reminiscent of intratumor heterogeneity in human cancers. Base
substitutions and evidence of DNA slippage near rearrangement breakpoints
revealed that translocation formation can be accompanied by point mutations, and
their presence in different translocation types within the same clone provides
evidence that some of the different translocation types are derived from each
other rather than being formed de novo. These findings provide
insight into eukaryotic genome instability, especially the formation of
translocations and the sources of intraclonal heterogeneity, both of which are
often associated with human cancers. 相似文献
103.
104.
105.
106.
Cuihua Wang Sofia Barluenga Girish K. Koripelly Jean-Gonzague Fontaine Ruihong Chen Jin-Chen Yu Xiaodong Shen John C. Chabala James V. Heck Allan Rubenstein Nicolas Winssinger 《Bioorganic & medicinal chemistry letters》2009,19(14):3836-3840
Pochoximes are potent inhibitors of heat shock protein 90 (HSP90) based on the radicicol pharmacophores. Herein we present a pharmacokinetics and pharmacodynamics evaluation of this compound series as well as a phosphate prodrug strategy to facilitate formulation and improve oral bioavailability. 相似文献
107.
108.
Summary During contests animals typically exchange information about fighting ability. Among feral horses these signals involve olfactory or acoustical elements and each type can effectively terminate contests before physical contact becomes necessary. Dung transplant experiments show that for stallions, irrespective of rank, olfactory signals such as dung sniffing encode information about familiarity suggesting that such signals can be used as signatures. As such they can provide indirect information about fighting ability as long as opponents associate identity with past performance. Play-back experiments, however, show that vocalizations, such as squeals, directly provide information about status regardless of stallion familiarity. Sonographs reveal that squeals of dominants are longer than those of subordinates and that only those of dominants have at their onset high-frequency components. 相似文献
109.
The selective regulation of Gs (long and short forms), Gi's (1, 2, and 3), and Go by the beta-adrenergic receptor was assessed quantitatively after coreconstitution of purified receptor, purified G-protein beta gamma subunits, and individual recombinant G-protein alpha subunits that were expressed in and purified from Escherichia coli. Receptor and beta gamma subunits were incorporated into phospholipid vesicles, and the alpha subunits bound to the vesicles stoichiometrically with respect to beta gamma. Efficient regulation of alpha subunit by receptor required the presence of beta gamma. Regulation of G proteins was measured according to the stimulation of the initial rate of GTP gamma S binding, steady-state GTPase activity, and equilibrium GDP/GDP exchange. The assays yielded qualitatively similar results. GDP/GDP exchange was a first-order reaction for each subunit. The rate constant increased linearly with the concentration of agonist-liganded receptor, and the dependence of the rate constant on receptor concentration was a reproducible measurement of the efficiency with which receptor regulated each G protein. Reconstituted alpha s (long or short form) was stimulated by receptor to approximately the extent described previously for natural Gs. Both alpha i,1 and alpha i,3 were regulated with 25-33% of that efficiency. Stimulation of alpha o and alpha i,2 was weak, and stimulation of alpha o was barely detectable over its high basal exchange rate. Reduction of the receptor with dithiothreitol increased the exchange rates for all G proteins but did not alter the relative selectivity of the receptor. 相似文献
110.
Chimpanzee fetal G gamma and A gamma globin gene nucleotide sequences provide further evidence of gene conversions in hominine evolution 总被引:5,自引:0,他引:5
The fetal globin genes G gamma and A gamma from one chromosome of a
chimpanzee (Pan troglodytes) were sequenced and found to be closely similar
to the corresponding genes of man and the gorilla. These genes contain
identical promoter and termination signals and have exons 1 and 2 separated
by the conserved short intron 1 (122 bp) and exons 2 and 3 separated by the
more rapidly evolving, larger intron 2 (893 bp and 887 bp in chimpanzee G
gamma and A gamma, respectively). Each intron 2 has a stretch of simple
sequence DNA (TG)n serving possibly as a "hot spot" for recombination. The
two chimpanzee genes encode polypeptide chains that differ only at position
136 (glycine in G gamma and alanine in A gamma) and that are identical to
the corresponding human chains, which have aspartic acid at position 73 and
lysine at 104 in contrast to glycine and arginine at these respective
positions of the gorilla A gamma chain. Phylogenetic analysis by the
parsimony method revealed four silent (synonymous) base substitutions in
evolutionary descent of the chimpanzee G gamma and A gamma codons and none
in the human and gorilla codons. These Homininae (Pan, Homo, Gorilla)
coding sequences evolved at one-tenth the average mammalian rate for
nonsynonymous and one-fourth that for synonymous substitutions. Three
sequence regions that were affected by gene conversions between chimpanzee
G gamma and A gamma loci were identified: one extended 3' of the hot spot
with G gamma replaced by the A gamma sequence, another extended 5' of the
hot spot with A gamma replaced by G gamma, and the third conversion
extended from the 5' flanking to the 5' end of intron 2, with G gamma
replaced here by the A gamma sequence. A conversion similar to this third
one has occurred independently in the descent of the gorilla genes. The
four previously identified conversions, labeled C1-C4 (Scott et al. 1984),
were substantiated with the addition of the chimpanzee genes to our
analysis (C1 being shared by all three hominines and C2, C3, and C4 being
found only in humans). Thus, the fetal genes from all three of these
hominine species have been active in gene conversions during the descent of
each species.
相似文献