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971.
Assay of mephenytoin metabolism in human liver microsomes by high-performance liquid chromatography 总被引:3,自引:0,他引:3
The metabolism of mephenytoin to its two major metabolites, 4-OH-mephenytoin (4-OH-M) and 5-phenyl-5-ethylhydantoin (nirvanol) was studied in human liver microsomes by a reversed phase HPLC assay. Because of preferential hydroxylation of S-mephenytoin in vivo, microsomes (5-300 micrograms protein) were incubated separately with S- and R-mephenytoin. After addition of phenobarbital as internal standard, the incubation mixture was extracted with dichloromethane. The residue remaining after evaporation was dissolved in water and injected on a 60 X 4.6-mm reversed-phase column (5 mu-C-18). Elution with acetonitrile/methanol/sodium perchlorate (20 mM, pH 2.5) led to almost baseline separation of mephenytoin, metabolites, and phenobarbital. Quantitation was performed by uv-absorption at 204 nm by the internal standard method. Propylene glycol was found to be the best solvent for mephenytoin, but inhibited the reaction noncompetitively. 4-OH-M and nirvanol could be detected at concentrations in the incubation mixture as low as 40 and 80 nM, respectively. The rates of metabolite formation were linear with time and protein concentration. The reaction was found to be substrate stereoselective. At substrate concentrations below 0.5 mM S-mephenytoin was preferentially hydroxylated to 4-OH-M, while R-mephenytoin was preferentially demethylated to nirvanol at all substrate concentrations tested (25-1600 microM). These data provide a mechanistic explanation for the stereospecific pharmacokinetics in vivo. The dependence of both metabolic relations on NADPH and the inhibition by CO suggest that they are mediated by cytochrome P-450-type monooxygenases.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
972.
Trends in economic traits, halothane sensitivity, blood group and enzyme systems of Swiss Landrace and Large White pigs 总被引:1,自引:0,他引:1
P V?geli D Schw?rer R Kühne M Wysshaar 《Animal blood groups and biochemical genetics》1985,16(4):285-296
Pigs deriving from 150 breeding centres constituting a representative section of elite breeding herds (2496 Swiss Landrace pigs, 587 Swiss Large White pigs) were subjected to blood typing during the period 1981 to 1984. Production traits such as daily gain, feed conversion ratio, lean meat content and meat quality score were available to show the trend in these performance traits since 1978. Field data on the halothane reaction of 14 270 Swiss Landrace (SL) pigs were used to assess the porcine stress syndrome during the period 1978-1983. In SL pigs the frequency of the alleles Ha, PhiB and AdaA decreased significantly, and that of the Hc and PhiA increased during the period of the study. The frequency of the Ha allele dropped from 0.36 in 1981 to 0.20 in 1984, whereas the Hc allele rose from 0.22 to 0.37. In Swiss Large White (SLW) pigs, on the other hand, the frequency of the Ha allele increased constantly from 0.31 to 0.37 during this period. An initial frequency of 17.7% (1978) halothane reactors in SL pigs was lowered to 0.7% (1982) after five years of halothane testing. In SL pigs the meat quality scores improved regularly, whereas in SLW pigs it did not change very much. The percentage of PSE animals in the SL breed was reduced from 32.7% in 1978 to 7.1% in 1983. Because the Hal locus is associated with production traits such as meat quality, linkage disequilibria could explain the observed associations between the H and Phi types and production traits. 相似文献
973.
Limited nonenzymatic glucosylation of low-density lipoprotein does not alter its catabolism in tissue culture 总被引:1,自引:0,他引:1
E Schleicher B Olgem?ller J Sch?n T Dürst O H Wieland 《Biochimica et biophysica acta》1985,846(2):226-233
This study examines the effects of various degrees of chemical modification of low-density lipoprotein (LDL) on its catabolism by various cell types. Moderate glucosylation of LDL does not alter its interaction with the high-affinity receptor present on human fibroblasts at concentration of 5-2000 micrograms LDL-cholesterol/ml. Only heavily glucosylated LDL (more than 12 lysine residues glucosylated per apolipoprotein B) or LDL glucosylated in the presence of Na(CN)BH3, i.e., conditions not expected to occur in diabetes, inhibit receptor-mediated internalisation and degradation. Moderately glucosylated LDL is also readily recognized by cultured rat hepatocytes and porcine endothelial cells. Human monocyte-derived macrophages accumulate cholesteryl ester when incubated with acetylated LDL for 12 days but no enhanced cholesteryl ester formation was found when native or glucosylated LDL (3.3 lysines glucosylated per apolipoprotein B) were used. 相似文献
974.
Transplasma-membrane redox systems in growth and development 总被引:19,自引:0,他引:19
975.
A sensitive analytical procedure for studying membrane-bound structures has been developed. Membrane glycoproteins inserted into liposomes were transferred to recipient cells by use of a lectin, concanavalin A, bound to the cells as a bridge to generate proximity between the recipient cell and the glycoprotein-containing liposome, prior to exposure to the fusing agent, poly(ethylene glycol). Partially purified histocompatibility antigen from rats was introduced into the membrane of human lymphocytes. After treating the cells with poly(ethylene glycol) under fusion conditions, some of the antigen present in the preparation could not be eluted with alpha-methyl mannoside and EDTA, indicating that incorporation in the cell membrane had taken place. This antigen remained exposed on the lymphocyte surface for approximately 1 h as demonstrated by sensitivity of the lymphocytes to the lytic effect of an antiserum to the histocompatibility antigen in the presence of complement. Some of the lectin molecules seemed to be internalized in the cells but no induction of cell mitosis was observed. The described method gives an opportunity to work with small amounts of membrane proteins inserted into liposomes, introducing them into recipient cells for analysis of their biological activities. 相似文献
976.
Chloride as allosteric effector of yeast aminopeptidase I 总被引:1,自引:0,他引:1
K H R?hm 《Archives of biochemistry and biophysics》1985,239(1):216-225
Activation of yeast aminopeptidase I by chloride was studied by kinetic methods. Several effects contributed to overall activity enhancement: At low concentrations of Zn2+ (an essential component of aminopeptidase I) chloride increased the amounts of active enzyme by reducing the cooperativity of metal binding. In addition, substrate turnover was enhanced due to increased kcat and a moderate decrease of Km. At high concentrations of Zn2+ substrate saturation curves were sigmoidal. Under these conditions chloride activated by restoring Michaelis-Menten kinetics of substrate turnover. At the same time, reconstitution of active enzyme from apoprotein and Zn2+ was substantially accelerated and its inactivation due to loss of Zn2+ was retarded. Co2+-Substituted aminopeptidase I, although catalytically active, was much less sensitive to chloride activation. Apparent binding constants for chloride, as estimated from its effects on metal binding and catalysis, respectively, were different. This suggests that two independent activation mechanisms may be operative. Both appear to be mediated by conformational changes of the enzyme protein. 相似文献
977.
By means of the transmissive and scanning electron microscopy methods and radioautography, structure of mucous membrane of the stomach and duodenum has been studied under experimentally induced duodenal ulcers before and after vagotomy during various time. The vagotomy results in accelerated healing of the ulcer defect. This is connected with an increased proliferative activity in the crypta cells, however, this is accompanied with deceleration of their differentiation. Under the duodenal ulcers the amount of chief and parietal cells increases in the gastric mucous membrane, this depends on gastrostasis produced by stenosis of the pylorus. At vagotomy the amount of the chief and parietal cells in the fundal glands of the mucous membrane decreases; this is accompanied with a lowered secretory activity. 相似文献
978.
Biosynthesis of the neural cell adhesion molecule: characterization of polypeptide C 总被引:15,自引:4,他引:11 下载免费PDF全文
O Nybroe M Albrechtsen J Dahlin D Linnemann J M Lyles C J M?ller E Bock 《The Journal of cell biology》1985,101(6):2310-2315
The biosynthesis of the neural cell adhesion molecule (N-CAM) was studied in primary cultures of rat cerebral glial cells, cerebellar granule neurons, and skeletal muscle cells. The three cell types produced different N-CAM polypeptide patterns. Glial cells synthesized a 135,000 Mr polypeptide B and a 115,000 Mr polypeptide C, whereas neurons expressed a 200,000 Mr polypeptide A as well as polypeptide B. Skeletal muscle cells produced polypeptide B. The polypeptides synthesized by the three cell types were immunochemically identical. The membrane association of polypeptide C was investigated with methods that distinguish peripheral and integral membrane proteins. Polypeptide C was found to be a peripheral membrane protein, whereas polypeptides A and B were integral membrane proteins with cytoplasmic domains of approximately 50,000 and approximately 25,000 Mr, respectively. The affinity of the membrane binding of polypeptide C increased during postnatal development. The posttranslational modifications of polypeptide C were investigated in glial cell cultures, and it was found to be N-linked glycosylated and sulfated. 相似文献
979.
An immunological approach to enrich a mitotic stimulator and to reveal G2-phase-specific proteins in Physarum polycephalum 下载免费PDF全文
Purified antibodies from an antiserum against S-phase proteins of the myxomycete Physarum polycephalum were attached to protein-A-Sepharose CL-4B. A late G2-phase extract that contained a mitosis-stimulating protein was applied to this immunoadsorbent, and the mitosis-stimulating protein was enriched by a factor of ten. This protein, which is present in the cell in low amounts, is synthesized in late G2 phase and obviously degraded in a later stage of the cycle. Immunoadsorption of a G2-phase extract with anti-S-antibodies decreased the 700 main proteins to 20 as demonstrated by two-dimensional gel electrophoresis. No difference in protein pattern could be observed on two-dimensional gels between S-phase and G2-phase extracts before and after immunoadsorption with anti-S-antibodies. This indicates that there are no G2-phase-specific proteins among the 700 most abundant proteins of Physarum polycephalum. 相似文献
980.