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11.
12.
A photosensitive derivative of glucagon, 125I-N?-4-azido-2-nitrophenyl-glucagon, has been synthesized and used to specifically label glucagon binding proteins in hepatocyte plasma membranes. Photolysis of the derivative in the presence of a membrane suspension results in the incorporation of radioactivity primarily into membrane components with a molecular weight range of 23,000–25,000. The binding properties of the derivative are essentially identical to that observed for glucagon. The binding of 125I-NAP-glucagon was completely inhibited in the presence of glucagon (3 μM) while greater than 90% of the covalent labeling was also inhibited in the presence of glucagon. These studies suggest that the labeled membrane protein may be a component of the glucagon receptor. 相似文献
13.
The fluorescence probe, 1,6-diphenyl-1,3,5-hexatriene, has been used to investigate the effects of controlled and uncontrolled growth on the dynamic properties of the lipid regions of hepatocyte plasma membranes. DPH was incubated with plasma membranes derived from quiescent and regenerating liver and Morris hepatoma 7777, and the resulting systems were studied by fluorescence polarization spectroscopy. Membranes from the rapidly growing hepatoma exhibited a significantly lower fluorescence polarization than observed in quiescent liver, suggesting the presence of a more fluid membrane lipid domain. Membranes from regenerating liver exhibited a time-dependent increase in membrane fluidity, reaching a maximum 12 h after growth stimulation. A close correspondence between membrane fluidity and the cholesterol-phospholipid ratio was also observed where a decrease in this ratio resulted in a more fluid lipid matrix. These results suggest that cell cycling, as observed in regenerating liver and Morris hepatoma 7777, results in significant increases in membrane fluidity, a property which may play an important regulatory role in various cell functions. 相似文献
14.
The synthesis of the diethylstilbestrol (DES) derivative with fluorine atoms present in the positions ortho to the hydroxyl in each ring is described. In vitro studies in a system containing horse radish peroxidase/H2O2 demonstrate extensive oxidation of tetrafluorodiethylstilbestrol to the corresponding dienestrol derivative. Tetrafluorodiethylstilbestrol and DES had comparable in vivo uterotropic activities at a dose of 100 microgram/kg. Competitive binding experiments demonstrated 20-25 fold reduced interaction with the mouse uterine estrogen receptor. This compound may be useful as an experimental estrogen in distinguishing between the biological and toxic effects of DES. 相似文献
15.
The effect of polyamines on the poly(adenylic acid)-induced inhibition of ribonuclease activity. 下载免费PDF全文
Segments of poly(A) at the 3'-termini of 5 S rRNA inhibit the activities of ribonucleases from Citrobacter, Enterobacter, bovine pancreas, human spleen and human plasma. Certain polyamines, or compounds containing polyamine substructures, mediate reversal of this inhibition. Effective compounds contain three amino groups, at least two of which are charged and are separated from the others by no less than three carbon atoms. Spermidine and 9-aminoacridines, which contain substituted propyl- or butylamino moieties at the 9-amino position and which bear two positive charges per molecule, are efficacious at low concentrations (5 microM). A decrease in effectiveness is associated with the removal of one aromatic ring from the 9-aminoacridines. However, the resulting 4-aminoquinolines, unlike the acridines, do not inhibit enzyme activity when present in concentrations above 30 microM. Relocating the diamino side chain from the 4- to the 8-position of the quinoline nucleus causes a decrease in charge density to +1, with the result that such compounds are ineffective. The orders of polyamine efficacy of reversal of inhibition were similar for enzymes from Citrobacter, bovine pancreas, and human plasma, and paralleled the order of binding of polyamines to either poly(A) or 5 S rRNA. This was not the case with Enterobacter and human spleen RNAases, indicating that the identity of the most effective polyamines depends on the RNAase studied. The combination of variable 3'-terminal poly(A) segment length and polyamine identity and concentration constitutes a system by which RNAase activities, and, therefore, substrate-degradation rates, may be easily varied. 相似文献
16.
Telomere end-replication problem and cell aging. 总被引:48,自引:0,他引:48
M Z Levy R C Allsopp A B Futcher C W Greider C B Harley 《Journal of molecular biology》1992,225(4):951-960
Since DNA polymerase requires a labile primer to initiate unidirectional 5'-3' synthesis, some bases at the 3' end of each template strand are not copied unless special mechanisms bypass this "end-replication" problem. Immortal eukaryotic cells, including transformed human cells, apparently use telomerase, an enzyme that elongates telomeres, to overcome incomplete end-replication. However, telomerase has not been detected in normal somatic cells, and these cells lose telomeres with age. Therefore, to better understand the consequences of incomplete replication, we modeled this process for a population of dividing cells. The analysis suggests four things. First, if single-stranded overhangs generated by incomplete replication are not degraded, then mean telomere length decreases by 0.25 of a deletion event per generation. If overhangs are degraded, the rate doubles. Data showing a decrease of about 50 base-pairs per generation in fibroblasts suggest that a full deletion event is 100 to 200 base-pairs. Second, if cells senesce after 80 doublings in vitro, mean telomere length decreases about 4000 base-pairs, but one or more telomeres in each cell will lose significantly more telomeric DNA. A checkpoint for regulation of cell growth may be signalled at that point. Third, variation in telomere length predicted by the model is consistent with the abrupt decline in dividing cells at senescence. Finally, variation in length of terminal restriction fragments is not fully explained by incomplete replication, suggesting significant interchromosomal variation in the length of telomeric or subtelomeric repeats. This analysis, together with assumptions allowing dominance of telomerase inactivation, suggests that telomere loss could explain cell cycle exit in human fibroblasts. 相似文献
17.
18.
19F nuclear magnetic resonance spectroscopy has been used to study the effects of salts and denaturants on the structure and aggregation properties of several trifluoroacetyl derivatives of insulin. This technique has been shown to be a powerful tool in the study of specific sites on the protein molecule. Circular dichroic and sedimentation velocity studies were also carried out to aid in the interpretation of the magnetic resonance data. At pH 6.8 Zn2+ had no effect on the 19F magnetic resonance spectrum, however, citrate and acetate ions significantly sharpened the signal from the trifluoroacetyl probe at the N-terminal end (glycine A-1) of the insulin A chain. No alterations were observed in the S20,W value of circular dichroic spectra, suggesting that the probe had gained a considerable degree of motional freedom without changes in aggregation or conformational properties. In the absence of perturbants the trifluoroacetyl group on glycine A-1 showed considerably more motional freedom than on phenylalanine B-1. Guanidine hydrochloride and sodium dodecyl sulfate were used to study the unfolding of several trifluoroacetylinsulin derivatives. The results suggested differential alterations in the environments of the probes located at glycine A-1, phenylalanine B-1, and lysine B-29 in the insulin molecule as the concentration of perturbant was increased. 相似文献
19.
Inhibition of the saturable influx of 0.05 mM 14C-labeled adenine or adenosine by AMP in adult Schistosoma mansoni in vitro suggested hydrolysis of this nucleotide at the tegumental surface of the parasite. Adenosine liberated as a result of AMP hydrolysis was the inhibitor of uptake of labeled adenine or adenosine. Inhibition of adenosine uptake by AMP or ATP was relieved by paranitrophenyl phosphate or ammonium molybdate supporting the hypothesis of nucleotide hydrolysis at the tengumental surface. Addition of glucose-1-phosphate, glucose-6-phosphate, NaF, or cysteine did not relieve AMP inhibition of adenosine uptake indicating substrate and inhibitor specificity for the surface enzyme(s). AMP, ATP, UMP, and p-nitrophenyl are hydrolyzed, at least in part, by the same enzyme(s). Apparent absorption of labeled AMP was preceded by hydrolysis, with labeled adenosine as the actual compound absorbed, although there was a small diffusion component for absorption of intact AMP. The site of nucleotide hydrolysis in close proximity to absorption sites provides a kinetic advantage for uptake of products of adenine nucleotide hydrolysis but not for products of uracil nucleotide hydrolysis. 相似文献
20.
We have previously described a monoclonal antibody, B16G, which has been found to be specific for T-cell derived suppressor factors (TsF). B16G has been shown to react with T-suppressor cells, TsF in the spleens of normal or tumor-bearing mice, the TsF produced by a tumor-specific T-cell hybridoma, and with polyclonal whole human TsF isolated from tonsilar tissue. This panreactivity inherent to the B16G MAb has made it clear that it recognizes some common, shared epitope of the TsF molecule. In this study we have used B16G as a probe to isolate TsF from the spleens of MRL-lpr mice and compare the activity with these factors isolated from the spleens of an MHC compatible nonautoimmune strain, CBA. We find that equivalent quantities of functional TsF are isolable from both strains and thus, it can be concluded that the associated oligoclonal B-cell activation characteristic of MRL-lpr mice is not due to a polyclonal T-suppressor cell deficit, nor to the ability of TsC in these mice to produce soluble, functional TsFs. The molecular and biochemical characteristics of these TsFs are discussed. 相似文献