全文获取类型
收费全文 | 86866篇 |
免费 | 2382篇 |
国内免费 | 46篇 |
专业分类
89294篇 |
出版年
2018年 | 921篇 |
2017年 | 1107篇 |
2016年 | 2852篇 |
2015年 | 6255篇 |
2014年 | 5856篇 |
2013年 | 5681篇 |
2012年 | 4861篇 |
2011年 | 2125篇 |
2010年 | 2142篇 |
2009年 | 2110篇 |
2008年 | 672篇 |
2007年 | 623篇 |
2006年 | 698篇 |
2005年 | 6788篇 |
2004年 | 5486篇 |
2003年 | 3655篇 |
2002年 | 1241篇 |
2001年 | 1161篇 |
2000年 | 389篇 |
1999年 | 1555篇 |
1998年 | 394篇 |
1997年 | 206篇 |
1992年 | 1978篇 |
1991年 | 2062篇 |
1990年 | 2140篇 |
1989年 | 2057篇 |
1988年 | 2009篇 |
1987年 | 1857篇 |
1986年 | 1679篇 |
1985年 | 1714篇 |
1984年 | 1149篇 |
1983年 | 880篇 |
1982年 | 499篇 |
1981年 | 466篇 |
1980年 | 401篇 |
1979年 | 1114篇 |
1978年 | 808篇 |
1977年 | 641篇 |
1976年 | 659篇 |
1975年 | 904篇 |
1974年 | 1026篇 |
1973年 | 1037篇 |
1972年 | 977篇 |
1971年 | 953篇 |
1970年 | 845篇 |
1969年 | 851篇 |
1968年 | 744篇 |
1967年 | 763篇 |
1966年 | 598篇 |
1965年 | 435篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
941.
942.
The miscibility properties of homologous cephalines (PEs) were studied by means of differential scanning calorimetry (DSC). The phase diagrams of 5 pseudo-binary cephaline/cephaline/water systems (50% water) are discussed. In the high temperature L alpha-phase, all the homologous cephalines of fatty acid chain length from C = 12 to C = 18 were completely miscible. On the other hand in the low temperature L beta-phase, a miscibility gap occurred in dependence on the differences of the acyl chain lengths. Further, a distinct succession of the phase diagram types was observed according to increasing chain length differences of the PEs: complete miscibility (systems di-(C12:O)-PE/di-(C14:O)-PE/H2O; di-(C14:O)-PE/di-C(16:O)-PE/H2O)----peritectic mixing behaviour (systems di-(C12:O)-PE/di-(C16:O)-PE/H2O; di-(C14:O)-PE/di-(C18:O)-PE/H2O)----eutectic mixing behaviour (system di-(C12:O)-PE/di-(C18:O)-PE/H2O). The change in the type of phase diagram from azeotropic to semi-azeotropic and from semi-azeotropic to eutectic is interpreted by means of the Landau theory. 相似文献
943.
For the first time fully protected substrates with only one hydrolyzable ester bond have been used to analyze the substrate specificity of microbial lipases. In these substrates the ester is attached to the glycerol molecule in a precisely defined position. The use of three different substituents generates chirality and thus allows the analysis of positional specificities of individual lipases. Therefore, these new substrates have been used to study the enzymatic activities of two closely related lipases isolated from Staphylococcus aureus (TEN5) designated the 44 and 43 kDa lipase. The lipases, especially the 44 kDa molecule, show a high specificity for the hydrolysis of the ester in the sn-1 position (S-configuration), which is hydrolyzed by a factor of ten faster than that in the sn-3 position. In addition, the study demonstrates for the first time that the rate of hydrolysis of a fatty acid ester attached to the sn-2 position of glycerol by microbial lipases depends on the configuration of the substrate molecule. 相似文献
944.
Dithiocarbamates can form lipid soluble complexes with lead and are known to markedly increase tissue uptake of lead and potentiate toxic effects of lead in rats. Cellular effects of the interactions between lead and diethyldithiocarbamate were studied in primary cultures of rat hepatocytes. The cells were incubated with lead acetate (PbAc) or lead-diethyldithiocarbamate complex (Pb(DTC)2), labelled with 203Pb. The lipid soluble Pb(DTC)2 was rapidly taken up in the cells and after 30 min incubation the cellular levels of lead were approximately 40 times higher in cells incubated with Pb(DTC)2 than in cells incubated with a similar concentration of PbAc. The maximal cellular uptake of lead was reached after 4 h incubation with Pb(DTC)2, while incubation with PbAc caused a slow continuously increasing uptake of lead during the 20 h incubation. The enzyme delta-aminolevulinic acid dehydratase (ALAD) was inhibited to a much higher extent by Pb(DTC)2 compared to PbAc after incubations with similar concentrations of lead. Maximal inhibition of ALAD activity was reached at a cellular concentration of 0.5-1 nmol Pb/mg protein, irrespective of which form of lead was used in the incubation. Pb(DTC)2 was shown to inhibit ALAD activity also in vitro when incubated with purified ALAD enzyme. The rapid and high intracellular uptake and cellular response of Pb(DTC)2, shown in the present study, may explain the drastic effects of dithiocarbamates on lead distribution and toxicity previously shown in vivo. 相似文献
945.
Malondialdehyde (MDA) excretion in urine as an index for toxicological effects of chloroform and hydroquinone was evaluated. In a first series of experiments three groups of rats were used: non-pretreated rats (group I), starved rats (group II) and starved plus phenobarbital pretreated rats (group III). Chloroform (0.15 or 0.30 ml/kg, p.o.) was given as a single dose. The MDA excretion was related to the pretreatment, and in group III to liver damage. In a second series of experiments control rats were administered hydroquinone (100 or 200 mg/kg, p.o.), which induced a dose-related MDA excretion. These data indicate that the MDA assay was a selective and accurate marker for toxicological effects induced by the tested compounds. 相似文献
946.
Identification of a bone sialoprotein receptor in osteosarcoma cells 总被引:12,自引:0,他引:12
A Oldberg A Franzén D Heineg?rd M Pierschbacher E Ruoslahti 《The Journal of biological chemistry》1988,263(36):19433-19436
Bone sialoprotein (BSP) is an extracellular matrix glycoprotein associated with the mineral bone matrix. The amino acid sequence of BSP contains an Arg-Gly-Asp (RGD) sequence which confers to the protein cell binding properties (Oldberg, A., Franzén, A., and Heineg?rd, D. (1988) J. Biol. Chem. 263, 19430-19432). When BSP was used as an affinity matrix to isolate a cell surface receptor from rat osteosarcoma cells, a protein composed of polypeptides similar in size to those of a previously characterized vitronectin receptor was obtained. This putative BSP receptor, like the vitronectin receptor, bound also to an affinity matrix made of an RGD-containing heptapeptide. Moreover, similar patterns of inhibition of cell attachment to BSP and vitronectin was obtained with variant RGD-containing peptides, with BSP and with vitronectin. Finally, an anti-vitronectin receptor antiserum immunoprecipitated a receptor identical in size to the receptor bound to a BSP affinity matrix. These results show that BSP is recognized by an RGD-directed receptor and that both vitronectin and BSP can bind to this receptor. 相似文献
947.
K Bostr?m J Borén M Wettesten A Sj?berg G Bondjers O Wiklund P Carlsson S O Olofsson 《The Journal of biological chemistry》1988,263(9):4434-4442
The relationship between apoB-100 and the membrane of the endoplasmic reticulum (ER) has been studied by a combination of pulse-chase methodology and subcellular fractionation. HepG2 cells were pulse-labeled with [35S]methionine for 3 min and chased with cold methionine for periods between 0 and 20 min. ApoB-100 and albumin, present in the membrane as well as in the luminal content of the ER vesicles, were isolated after each chase period. The results indicated that apoB-100 was cotranslationally bound to the membrane of the ER, and from this membrane-bound form, was transferred to the lumen after a delay of 10-15 min. Albumin was, as could be expected for a typical secretory protein, cotranslationally sequestered in the lumen of the ER. Apo-B-100-containing lipoproteins present in the microsomal lumen were analyzed by ultracentrifugation in a sucrose gradient. ApoB-100 occurred on rounded particles in three density regions: (i) d 1.1065-1.170 g/ml (Fraction I), (ii) d 1.011-1.045 g/ml (Fraction II), and (iii) d less than 1.011 g/ml (Fraction III). Fraction I, isolated from cells cultured in the absence of oleic acid, contained a homogenous population of particles with a mean diameter of approximately 200 A. Fraction I isolated from cells cultured in the presence of oleic acid was slightly more heterogeneous and had a mean diameter of approximately 250 A. Fractions II and III had mean diameters of 300 and 500 A, respectively. Cholesterol esters and triacylglycerol were the quantitatively dominating lipid constituents of all three fractions. Pulse-chase experiments indicated that Fraction I contained the newly assembled lipoproteins. With increasing chase time, the apoB-100 radioactivity was redistributed from Fraction I to Fractions II and III, indicating that Fraction I is converted into Fractions II and III during the intracellular transfer. Particles corresponding to Fractions II and III were by far the most abundant lipoproteins found in the medium. The results presented support the possibility of a sequential assembly of apoB-100-containing lipoproteins. 相似文献
948.
R G Painter R Dukes J Sullivan R Carter E G Erd?s A R Johnson 《The Journal of biological chemistry》1988,263(19):9456-9461
Intact human neutrophils hydrolyzed N-formyl-Met-Leu-[3H]Phe (fMLP) and released Leu-[3H]Phe, cleaving 45-50% of the peptide within 20 min at 37 degrees C. The dipeptide after its release was then hydrolyzed to free amino acids by a dipeptidase (EC 3.4.13.11). This activity, present in plasma membrane-enriched fractions of neutrophil lysates, was also inhibited over 90% by phosphoramidon, an inhibitor of neutral endopeptidase (NEP, EC 3.4.24.11). Dithiothreitol and EDTA inhibited the activity to a comparable degree, suggesting the requirement for a heavy metal cofactor. Bestatin and amastatin, inhibitors of aminopeptidases (but not human kidney NEP), did not inhibit the rate of fMLP degradation but prevented the production of free phenylalanine and enhanced the accumulation of Leu-Phe. Of other inhibitors, alpha 1-antitrypsin and alpha 2-macroglobulin slightly enhanced the rate of fMLP hydrolysis by neutrophils, and others tested were ineffective. Rabbit antiserum to homogeneous human kidney NEP reacted specifically with a 100-kDa protein present in sodium dodecyl sulfate-solubilized neutrophils. The Mr of this protein was slightly larger than that of the kidney enzyme in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The antiserum incubated with intact cells specifically inhibited the degradation of fMLP over 70%. First, we confirm that NEP present on the plasma membrane cleaves fMLP at the Met-Leu bond; then the dipeptide Leu-Phe is cleaved by a dipeptidase. Finally, inhibition of NEP completely blocks fMLP-mediated chemotaxis. Thus, the enzyme may play an important role in modulating chemotactic responses. 相似文献
949.
We have investigated here the pre-steady state kinetics of sarcoplasmic reticulum ATPase incubated under conditions where significant amounts of Mg.ATP and Ca.ATP coexist, both of them being substrates for the ATPase. We confirmed that these two substrates are independently hydrolyzed by the ATPase, which thus apparently catalyzes Pi production by two simultaneous and separate pathways. External calcium (or the Ca2+/Mg2+ ratio) determines the extent to which Ca2+ or Mg2+ is bound at the phosphorylation site, while internal calcium controls the rate of processing of both the slow, calcium-containing and the fast, magnesium-containing phosphoenzyme. Time-dependent binding of calcium at the catalytic site is correlated with the observed burst of Pi liberation, which therefore results from reequilibration during pre-steady state of magnesium- and calcium-containing phosphoenzyme pools. Independently of direct exchange of metal at the catalytic site, ADP produced by the hydrolysis reaction contributes to reequilibration of these pools through reversal of phosphorylation by the ATP-ADP exchange pathway. 相似文献
950.
A polarized epithelial cell mutant deficient in translocation of UDP-galactose into the Golgi complex 总被引:17,自引:0,他引:17
A W Br?ndli G C Hansson E Rodriguez-Boulan K Simons 《The Journal of biological chemistry》1988,263(31):16283-16290
Two lectin-resistant mutants derived from a polarized epithelial cell line have been described (Meiss, H.K., Green, R.F., and Rodriguez-Boulan, E.J. (1982) Mol. Cell. Biol. 2, 1287-1294). One of these mutants, the Madin-Darby canine kidney strain II cell line resistant to Ricinus communis agglutinin (MDCKII-RCAr), has been further characterized, and the biochemical defect leading to its altered phenotype has been determined. MDCKII-RCAr cells are shown to be enriched in cell-surface glycoconjugates bearing terminal N-acetylglucosamine residues by in vitro exogalactosylation and by labeling with fluorescent lectins. Binding assays with a sialic acid-specific lectin reveal a 70-75% reduction in sialylation of cell-surface glycoconjugates. The defect is pleiotropic in nature, affecting glycoproteins as well as glycosphingolipids. Analysis of glycosphingolipids shows a strong reduction of galactose-containing glycosphingolipids. Almost 90% of the glycosphingolipids are identified as glucosyl-ceramide. The mutant is not deficient in galactosyl- and sialytransferase activities. However, Golgi vesicles isolated from MDCKII-RCAr cells translocate UDP-galactose at only 2% of the rate observed for vesicles from wild-type MDCKII cells. The deficiency is specific, because translocation rates of UDP-N-acetylglucosamine and CMP-sialic acid are comparable for vesicles isolated from MDCKII-RCAr cells and wild-type cells. Despite the inability to translocate UDP-galactose into the lumen of the Golgi apparatus, MDCKII-RCAr cells are able to form monolayers with normal apical and basolateral polarity as shown by plasma membrane domain-restricted exogalactosylation. 相似文献