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41.
Michael Böhm 《Molecular and cellular biochemistry》1995,147(1-2):147-160
Alterations of receptor-G-protein-regulated adenylyl cyclase activity have been suggested to represent an important alteration leading to contractile dysfunction in the failing human heart. Recent experiments suggest that the 1-adrenoceptor(1AR) density and mRNA levels are reduced, while 2-adrenoceptors and stimulatory G-proteins are unchanged (mRNA and protein level). Functional assays demonstrated that the catalyst of the adenylyl cyclase is not different between failing and nonfailing myocardium. Inhibitory G-proteins are increased (pertussis toxin substrates, protein and mRNA) and correlate to the reduced inotropic effects of -adrenoceptor agonists and of CAMP-PDE inhibitors. Gi-coupled m-cholinoceptors and A1-adrenergic receptors are unchanged in density and affinity. Stimulation of these receptors resulted in an unchanged antiadrenergic effect on force of contraction. In conclusion, a downregulation of 1-AR and an increase of Gi have been observed as signal transduction alteration in failing human myocardium. These alterations are due to alterations of gene expression in the failing heart and are related to a defective regulation of force of contraction in heart failure. 相似文献
42.
Transglutaminase catalyzes the intermolecular cross-linking of peptides between Gln and Lys residues, forming an -(-glutamyl) lysine bond. Amyloid -peptide, a major constituent of the deposits in Alzheimer disease, contains Lys16, Lys28, and Gln15 which may act as substrates of transglutaminase. Transglutaminase treatment of amyloid -peptide (1–28) and amyloid -peptide (1–40) yielded cross-linked oligomers. Transglutaminase-treated A retarded neurite extension of PC12 cells, and rat cultured neurons of hippocampus and septum, brain areas severely affected by Alzheimer disease, and subsequently caused cell death, whereas the transglutaminase-untreated counterparts did not show harmful effects. The transglutaminase-catalyzed oligomers of amyloid -peptide and their neurotoxicity may be involved in two characteristics in Alzheimer disease, neuronal degeneration and formation of the insoluble deposits.Abbreviations: AD – Alzheimer disease, A – amyloid -peptide, DMEM – Dulbecco's modified Eagle's medium, DMEM/F–12–1:1 mixture of DMEM and Ham's F–12 medium, FCS – fetal calf serum, HS – horse serum, PAGE – polyacrylamide gel electrophoresis, MTT – 3-(4,5-dimethylthiazol–2-yl)–2,5-diphenyltetrazolium bromide, NGF – nerve growth factor, TGase – transglutaminase. 相似文献
43.
Ave Patrick Colucci-Guyon Emma Babinet Charles Huerre Michel-Rene 《Transgenic research》1997,6(1):37-40
The Escherichia coli -galactosidase gene is frequently used as a reporter gene in transgenic studies because its activity can be easily detected at the cellular level. Here we report a procedure for monitoring -galactosidase activity directly in tissue sections, which involves the use of a mixture of ethanol and poly-ethylene-glycol as a fixative (Kryofix) and a special paraffin characterized by a lower fusion point of 42 °C. After embedding and cutting, the sections are stained by the chromogenic substrate 5-bromo-4-chloro-3-indoyl--d galactopyranoside (X-Gal). This procedure allows both the retention of a high level of -galactosidase activity and the preservation of good tissue morphology. Furthermore, it can be combined with immunohistochemical methods to detect other cellular components without compromising reporter gene detection 相似文献
44.
The effects of the calmodulin antagonists W-7 and trifluoperazine have been measured on the Ca2+-activated potassium channel in the membrane surrounding protoplasmic drops expressed from internodal cells of charophyte
plants. The large-conductance (170 pS), voltage- and Ca2+-dependent gating, and prominent conductance substrate of this channel shows a strong kinetic resemblance to those of the
Maxi-K channel from animal cells.
This is the first study of the action of calmodulin antagonists which measures their effects on the most populated substates
as well as the closed and main open states of Maxi-K channels. The substate analysis provides new evidence for different modes
of action of- and different bindings sites for these calmodulin antagonists.
Neither antagonist produces the simple closure of the channel reported previously as its effect on the Maxi-K channel, though
both do induce flicker-block, reducing the mean current to near zero at high concentrations following an inverted Michaelis-Menten
curve.
W-7 reduces residence time in the fully open state, thus raising, in the same proportions, the probabilities of finding the
channel in the closed state or a pre-existing substate. Its binding to the channel is voltage- and calcium-dependent.
In contrast, trifluoperazine reduces residence in the open state and promotes an apparently new substate which overlaps the
closed state at −50 mV but is distinguishable from it at voltages more negative than −100 mV. This substate may represent
times that trifluoperazine is bound to the channel.
Both antagonists have effects clearly distinguishable from that of withdrawing calcium from the channel, which does not affect
open state residence time but increases closed state residence time. Thus neither antagonist reverses the activating effect
of Ca2−. This is good kinetic evidence against the view that the channel is activated by Ca2+-calmodulin and that the effect of a calmodulin antagonist is to reverse this process by making Ca2−-calmodulin less available.
Received: 26 August 1996/Revised: 7 October 1996 相似文献
45.
J D Zajac S A Livesey T J Martin 《Biochemical and biophysical research communications》1984,122(3):1040-1046
When the F1-ATPase from the thermophilic bacterium, PS3, was inactivated by 90% with 7-chloro-4-nitro[14C]benzofurazan ([14C]Nbf-Cl) at pH 7.3 and then gel-filtered, 1.25 mols of [14C]Nbf-O-Tyr and less than 0.1 mol of Nbf-N-Lys were formed per mol of enzyme. After adjusting the pH of the gel-filtered, modified enzyme to 9.0 and incubating it for 14 hrs. at 23 degrees C to promote O----N migration, 0.68 mol of Nbf-N-Lys were formed per mol of enzyme while about 16% of the original activity reappeared. Isolation of the subunits after the O----N migration showed that 90% of the incorporated 14C was present in the beta subunit, which contained 0.21 mols of [14C]Nbf-N-Lys per mol. A tryptic peptide which contained the majority of the 14C incorporated into the beta subunit was isolated and subjected to automatic amino acid sequence analysis contained 38 residues. The amino acid sequence immediately around the lysine residue labeled with [14C]Nbf-, K*, was found to be: ...I-G-L-F-G-G-A-G-V-G-K*-T-V-L-I-G... . 相似文献
46.
Patricia E. Gallagher Thomas P. Brent 《Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression》1984,782(4):394-401
Further purification of a human placental 3-methyladenine-DNA glycosylase by phosphocellulose column chromatography yielded a 6000-fold increase in specific activity with greater than 5% recovery. Although 3-methyladenine was the predominant base released from double-stranded methylated DNA by this enzyme, minor releasing activities for 7-methylguanine and 3-methylguanine were also observed. During purification, the three DNA glycosylase activities consistently copurified with constant ratios of specific activity. Moreover, all the activities were heat-inactivated at 50°C at the same rate, required double-stranded methylated DNA as substrate, were inhibited by spermine and spermidine, and were not subject to product inhibition. These data strengthen the likelihood that the three activities are associated with a single DNA glycosylase. 相似文献
47.
Abstract The time course of photobleaching and the nanosecond fluorescence decay have been measured from microscopic samples of methanogenic bacteria, to our knowledge the first application of these methods in this field. Decay times of about 1 ns and 3 ns were obtained for the specific coenzymes F420 and 7-methylpterin, respectively. In contrast to methylpterin and other fluorescent compounds the intensity of F420 fluorescence was reduced selectively due to photobleaching. This effect, as well as the different decay time constants could be used to discriminate F420 from other fluorescent components. In addition, active and inactive bacterial cells could be differentiated following the course of photobleaching. 相似文献
48.
49.
Human β-glucuronidase: Assignment of the structural gene to chromosome 7 using somatic cell hybrids 总被引:1,自引:0,他引:1
P. A. Lalley J. A. Brown R. L. Eddy L. L. Haley M. G. Byers A. P. Goggin T. B. Shows 《Biochemical genetics》1977,15(3-4):367-382
-Glucuronidase (GUS) has become an important enzyme model for the genetic study of molecular disease, enzyme realization, and therapy, and for the biogenesis and function of the lysosome and lysosomal enzymes. The genetics of human -glucuronidase was investigated utilizing 188 primary man-mouse and man-Chinese hamster somatic cell hybrids segregating human chromosomes. Cell hybrids were derived from 16 different fusion experiments involving cells from ten different and unrelated individuals and six different rodent cell lines. The genetic relationship of GUS to 28 enzyme markers representing 19 linkage groups was determined, and chromosome studies on selected cell hybrids were performed. The evidence indicates that the -glucuronidase gene is assigned to chromosome 7 in man. Comparative linkage data in man and mouse indicate that the structural gene GUS is located in a region on chromosome 7 that has remained conserved during evolution. Involvement of other chromosomes whose genes may be important in the final expression of GUS was not observed. A tetrameric structure of human -glucuronidase was demonstrated by the formation of three heteropolymers migrating between the human and mouse molecular forms in chromosome 7 positive cell hybrids. Linkage of GUS to other lysosomal enzyme genes was investigated. -Hexosaminidase HEX
B) was assigned to chromosome 5; acid phosphatase2
(ACP
2) and esterase A4
(ES-A
4) were assigned to chromosome 11; HEX
A was not linked to GUS; and -galactosidase (-GAL) was localized on the X chromosome. These assignments are consistent with previous reports. Evidence was not obtained for a cluster of lysosomal enzyme structural genes. In demonstrating that GUS was not assigned to chromosome 9 utilizing an X/9 translocation segregating in cell hybrids, the gene coding for human adenylate kinase1 was confirmed to be located on chromosome 9.Supported by NIH Grants HD 05196, GM 20454, and GM 06321, by NSF Grant BMS 73-07072, and by HEW Maternal and Child Health Service, Project 417. 相似文献
50.
Five C-glycosylflavonoids including two new compounds, isovitexin 7-rhamnosylglucoside and isomollupentin 7-rhamnosylglucoside, were obtained from the leaves of Passiflora platyloba. The known flavonoids were isovitexin, vitexin and isomollupentin (6-C-arabinosylapigenin). In addition, the coumarin esculetin was isolated. 相似文献