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141.
Pseudo-peptide bond inhibitors (-bond inhibitors) and peptide-aldehyde inhibitors of atrial granule serine proteinase, the candidate processing enzyme of pro-atrial natrieuretic factor, are prepared in high yield and purity by novel synthetic routes. The -bond compounds retain essential residues for enzyme binding, but place the enzyme inhibition site in the midst of the peptide sequence. Thus, Bz-APR--LR and Bz-APR--SLRR can be considered readthrough inhibitors of atrial granule serine proteinase. The most potent -peptide, Bz-APR--SLRR (IC50=250 M), is about fivefold less potent than the best peptide-aldehyde inhibitor (EACA-APR-CHO), and both the -bond and peptide-aldehyde compounds are competitive, reversible inhibitors of the enzyme. The -bond peptides containing two C-terminal Arg residues are three-to tenfold more potent than the analogous compounds containing only one C-terminal Arg residue, confirming the importance of both Arg residues in the enzyme processing recognition site. As expected, because of their moderate potencies, the -peptides are not useful affinity ligands for purification of atrial granule serine proteinase, but both peptide aldehydes are effective affinity ligands [Damodaran and Harris (1995),J. Protein Chem., this issue].Abbreviations AGSP
atrial granule serine proteinase
- ANF
atrial natriuretic factor
- Bz
benzoyl
- DIEA
diisopropylethylamine
- DIPCDI
diisopropylcarbodiimide
- DMF
dimethylformamide
- DMSO
dimethylsulfoxide
- EACA
6(e)-aminocaproic acid
- EtOAc
ethyl acetate
- HEPES
N-2-hydroxyethylpiperazine-N-propanesulfonic acid
- HOBt
N-hydroxybenzotriazole
- HPLC
high-performance liquid chrornatography
- NMR
nuclear magnetic resonance
- PEG
polyethylene glycol-3350
- PyBOP
benzotriazole-1-yl-oxy-trispyrrolidino-phosphonium-hexafluorophospate
- TEA
triethylamine
- TFA
trifluoroacetic acid
- THF
tetrahydrofuran
- TLC
thin-layer chromatography
- UV
ultraviolet
-
pseudo-peptide bond -CH2-NH-. Single-letter abbreviations are used to denote amino acids 相似文献
142.
The Uba2 and Ufd1 proteins of Saccharomyces cerevisiae interact with poly(A) polymerase and affect the polyadenylation activity of cell extracts 总被引:2,自引:0,他引:2
Poly(A) polymerase is responsible for the addition of the adenylate tail to the 3′ ends of mRNA. Using the two-hybrid system,
we have identified two proteins which interact specifically with the Saccharomyces cerevisiae poly(A) polymerase, Pap1. Uba2 is a homolog of ubiquitin-activating (E1) enzymes and Ufd1 is a protein whose function is probably
also linked to the ubiquitin-mediated protein degradation pathway. These two proteins interact with Pap1 and with each other,
but not with eight other target proteins which were tested in the two-hybrid system. The last 115 amino acids of Uba2, which
contains an 82-amino acid region not present in previously characterized E1 enzymes, is sufficient for the interaction with
Pap1. Both Uba2 and Ufd1 can be co-immunoprecipitated from extracts with Pap1, confirming in vitro the interaction identified
by two-hybrid analysis. Depletion of Uba2 from cells produces extracts which polyadenylate precursor RNA with increased efficiency
compared to extracts from nondepleted cells, while depletion of Ufd1 yields extracts which are defective in processing. These
two proteins are not components of polyadenylation factors, and instead may have a role in regulating poly(A) polymerase activity.
Received: 6 January 1997 / Accepted: 27 February 1997 相似文献
143.
Astrid Schön 《Molecular biology reports》1995,22(2-3):139-145
RNase P consists of both protein and RNA subunits in all organisms and organelles investigated so far, with the exception of chloroplasts and plant nuclei where no enzyme-associated RNA has been detected to date. Studies on substrate specificity revealed that cleavage by plant nuclear RNase P is critically dependent on a complete and intact structure of the substrate. No clearcut answer is yet possible regarding the order of processing events at the 5 or 3 end of tRNAs in the case of nuclear or chloroplast processing enzymes. RNase P from a phylogenetically ancient photosynthetic organelle will be discussed in greater detail: The enzyme from theCyanophora paradoxa cyanelle is the first RNase P from a photosynthetic organelle which has been shown to contain an essential RNA subunit. This RNA is strikingly similar to its counterpart from cyanobacteria, yet it lacks catalytic activity. Properties of the holoenzyme suggest an intermediate position in RNA enzyme evolution, with an eukaryotic-type, inactive RNA and a prokaryotic-type small protein subunit. The possible presence of an RNA component in RNase P from plant nuclei and modern chloroplasts will be discussed, including a critical evaluation of some criteria that have been frequently applied to elucidate the subunit composition of RNase P from different organisms.Abbreviations RNase P
Ribonuclease P
- (pre-)tRNA
transfer ribonucleic acid (precursor)
- tRNA
Ser
(-
Tyr
, -
Phe
)
transfer ribonucleic acid specific for serine (tyrosine, phenylalanine)
- CyRP RNA
RNA component of cyanelle RNase P 相似文献
144.
Walter R. A. van Heumen Gregg T. Nagle Alexander Kurosky 《Cell and tissue research》1995,279(1):13-24
The atrial gland is an exocrine organ that secretes into the oviduct of Aplysia californica and expresses three homologous genes belonging to the egglaying hormone gene family. Although post-translational processing of the egg-laying hormone precursor in the neuroendocrine bag cells has been examined in detail, relatively little is known about the post-translational processing of egg-laying hormone-related gene products in the atrial gland. A combination of morphologic techniques that included light-microscopic histology and immunocytochemistry, transmission electron microscopy, and immuno-electron microscopy were used to localize egg-laying hormone-related peptides in the atrial gland and to evaluate the characteristic morphology of their secretory cells. Results of these studies showed that there were at least three major types of secretory cells in the atrial gland (types 1–3). Significantly, of these three cell types, only type 1 was immunoreactive to antisera against egg-laying hormone-related precursor peptides. The immunoreactivity studies established that all three egg-laying hormone-related precursor genes are expressed in type-1 cells and indicated that the processing of these precursors also occurs within the secretory granules of this cell type. Evidence was also obtained that proteolytic processing of the egg-laying hormone-related precursors differed significantly from that observed in the bag cells. In contrast to the bag cells, the NH2-terminal and COOH-terminal products of the egg-laying hormone-related precursors of the atrial gland were not sorted into different types of vesicles. 相似文献
145.
R. C. Roverud 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1995,176(1):1-9
A stereotyped approach phase vocalization response of Noctilio albiventris to artificial echoes simulating a virtual approaching object was used to assess the ability of the bat to analyze and extract distance information from the artificial echoes. The performance of the bats depended on the temporal pattern of frequency change of the continuously sweeping frequency modulated (FM) component of the signals. When the bats were presented with a CF/FM signal containing a time-reversed upward FM sweep, they responded with approach phase behavior at a performance level that was significantly below that seen with a CF/FM signal containing a naturally structured downward FM sweep. When the FM sweep was divided into a series of brief pure tone steps, the extent to which the bats showed a difference in their capability to process upward versus downward FM sweeps depended on the difference in frequency between the pure tone steps. The bats effectively processed downward but not upward FM sweeps when the difference in frequency between pure tone frequency elements of the FM sweeps was from about 100–200 Hz, but they effectually processed both downward and upward FM sweeps when the tonal elements composing the FM sweeps were separated by more than about 200 Hz. This suggests that the ability of the bats to effectively process downward but not upward FM sweeps is based on local interactions between adjacent frequency elements of the complex sounds.Abbreviations
CF
constant frequency
-
FM
frequency modulated 相似文献
146.
The stable bacteriocin release protein signal peptide, expressed as a separate entity, functions in the release of cloacin DF13 总被引:3,自引:0,他引:3
Fimme J. van der Wal Corinne M. ten Hagen Bauke Oudega Joen Luirink 《FEMS microbiology letters》1995,131(2):173-177
Abstract The pCloDF1S encoded bacteriocin release protein (BRP) plays a role in the release of the bacteriocin cloacin DF13. The BRP signal peptide is stable after cleavage, and accumulates in the cytoplasmic membrane. A BRP which is correctly targeted by the unstable murein lipoprotein signal peptide (Lpp-BRP) is not capable of inducing the release of cloacin DF13. To investigate the role of the stable BRP signal peptide in the release of cloacin DF13, the stable BRP signal peptide and the Lpp-BRP were expressed in trans in cells also producing cloacin DF13. Expression and release experiments indicate that the stable signal peptide can complement the Lpp-BRP in the release of cloacin DF13. 相似文献
147.
Endocrine cell cultures have potential in bioprocessing, for the production of biologically active hormones, and in tissue engineering, for the development of implantable artificial tissues for long-term restoration of endocrine function. To optimize such systems, it is necessary to develop a thorough understanding of how inherently present environmental stresses, such as nutrient depletion and metabolite accumulation, affect the cells. This work focuses on the effects of the metabolite ammonium on indicators of endocrine cell metabolism and on the processing, storage and secretion of regulated secretory proteins. Experiments were conducted on recombinant insulin-producing mouse pituitary AtT-20 cells and mouse insulinoma TC3 cells. Exposure for 24–48 hours to 6 mM of exogenous ammonium resulted in higher rates of glucose consumption by both AtT-20 and TC3 cells, while the formation of additional ammonium generally decreased relative to ammonium-free controls. When TC3 cells were discharged of their intracellular insulin stores, the presence of ammonium during a subsequent recharge completely inhibited addition of new insulin-related peptides to the stores, as we had observed previously for both cell lines. There was a correlation between insulin-related peptides stored in TC3 cells during recharging and the amount that could be released upon secretagogue stimulation. Using a combination of radioimmunoassay and high performance liquid chromatography, we found that intracellular insulin and insulin-related peptides changed in the same fashion. Intracellular mechanisms that may be producing the observed results are discussed.Abbreviations IRP
insulin-related peptides
- HPLC
high performance liquid chromatography
- DAMP
3-(2,4-dinitroanilino)-3 amino-N-methyldipropylamine 相似文献
148.
Two series of amino-modified silicate gels prepared by sol-gel processing were used to absorb Cu(II), Ni(II), Co(II), Mn(II) and Cr(III) from aqueous solutions. These easily prepared sorbents with various content of primary amino groups in series (A) or primary and secondary amino groups in series (AA) have reasonable stability. The gel composition, time and concentration dependence of the uptake of the metal ions by these materials were studied systematically. These materials would be further used as supports to disperse catalytically active phases by conventional wet chemical procedures. Apart from this they demonstrate potential for the preconcentration aid for transition metal analysis. 相似文献
149.
Gerd Maulthaup Hans Mechler Colin L. Masters 《Journal of molecular recognition : JMR》1995,8(4):247-257
The Alzheimer's disease βA4 amyloid precursor protein (APP) has been shown to be involved in a diverse set of biological protein precursor-like proteins (APLP1 and APLP2) belong to a superfamily of proteins that are probably functionally related. In order to characterize the cell adhesion properties of APP the brain specific isoform APP695 was purified and used to assess the binding to herparin, a structural and functional analogue of the glycosaminoglycan heparan sulfate. We show that APP binds in a time dependent and saturable manner to heparin. The salt concentration of 620 mM at which APP elutes from heparin Sepharose is greater than physiological. Tha apparent equilibrium constant for dissociation was determined to be 300 pM for APP binding to heparin Sepharose. A high affinity heparin binding site was identified within a region conversed in rodent and human APP, APLP1 and APLP2. This binding site was located between residues 316-337 of APP695 which is within the carbohydrate domain of APP. We also demonstrate an interaction between this heparin binding site and the zinc(II) binding site which is conserved in all members of the APP superfamily. We show by using an automated surface plasmon resonance biosensor (BIAcore, Pharmacia) that the affinity for heparin is increased two- to four-fold in the presence of micromolar zinc(II). The identification of zinc-enhanced binding of APP to heparin sulfate side chains of proteoglycans offers a molecular link between zinc(II), as a putative environmental toxin for Alzheimer's disease, and aggregation of amyloid βA4 protein. 相似文献
150.
A simple and sensitive chemical assay was developed for 1-aminocyclopropane-1-carboxylic acid (ACC), a precursor of ethylene. The assay is based on the liberation of ethylene from ACC at pH 11.5 in the presence of pyridoxal phosphate, MnCl2 and H2O2. This assay was used to detect ACC in extracts of tomato fruits (Lycopersicon esculentum Mill.) and to measure the activity of a soluble enzyme from tomato fruit that converted S-adenosylmethionine (SAM) to ACC. The enzyme had a Km of 13 M for SAM, and conversion of SAM to ACC was competitively and reversibly inhibited by aminoethoxyvinylglycine (AVG), an analog of rhizobitoxine. The Ki value for AVG was 0.2 M. The level of the ACC-forming enzyme activity was positively correlated with the content of ACC and the rate of ethylene formation in wild-type tomatoes of different developmental stages. Mature fruits of the rin (non-ripening) mutant of tomato, which only produce low levels of ethylene, contained much lower levels of ACC and of the ACC-forming enzyme activity than wild-type tomato fruits of comparable age.Abbreviations ACC
1-aminocyclopropane-1-carboxylic acid
- AVG
ammoethoxyvinylglycine, the aminoethoxy analog of rhizobitoxine L-2-amino-4-(2-aminoethoxy)-trans-3-butenoic acid
- SAM
S-adenosyl-L-methionine
Michigan Agricultural Experiment Station No. 8876 相似文献