全文获取类型
收费全文 | 3394篇 |
免费 | 263篇 |
出版年
2024年 | 1篇 |
2023年 | 5篇 |
2022年 | 14篇 |
2021年 | 59篇 |
2020年 | 24篇 |
2019年 | 29篇 |
2018年 | 43篇 |
2017年 | 35篇 |
2016年 | 88篇 |
2015年 | 110篇 |
2014年 | 149篇 |
2013年 | 222篇 |
2012年 | 261篇 |
2011年 | 247篇 |
2010年 | 184篇 |
2009年 | 166篇 |
2008年 | 228篇 |
2007年 | 239篇 |
2006年 | 220篇 |
2005年 | 186篇 |
2004年 | 219篇 |
2003年 | 206篇 |
2002年 | 195篇 |
2001年 | 33篇 |
2000年 | 36篇 |
1999年 | 38篇 |
1998年 | 87篇 |
1997年 | 46篇 |
1996年 | 44篇 |
1995年 | 36篇 |
1994年 | 34篇 |
1993年 | 32篇 |
1992年 | 22篇 |
1991年 | 22篇 |
1990年 | 11篇 |
1989年 | 14篇 |
1988年 | 15篇 |
1987年 | 7篇 |
1986年 | 5篇 |
1985年 | 6篇 |
1984年 | 9篇 |
1983年 | 2篇 |
1982年 | 9篇 |
1981年 | 9篇 |
1980年 | 3篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1975年 | 2篇 |
排序方式: 共有3657条查询结果,搜索用时 156 毫秒
41.
J. Custot Jean-Luc Boucher Sandrine Vadon Catherine Guedes Sylvie Dijols Marcel Delaforge Daniel Mansuy 《Journal of biological inorganic chemistry》1996,1(1):73-82
The effects of various compounds bearing an N-OH group such as N-hydroxy-guanidines, amidoximes, and hydroxylamines, on bovine and rat liver arginases was studied. Some of these compounds
with an l-α-amino acid function at an appropriate distance from the N-OH group acted as strong competitive liver arginase inhibitors,
displaying Ki values between 4 and 150 μM. Two compounds, N
ε-hydroxy-l-lysine and N
ω-hydroxy-d,l-indospicine, which exhibited Ki values of 4 and 20 μM (at pH 7.4), were the most potent inhibitors of arginase described
to date. The distance between the α-amino acid and N-OH functions appeared to be crucial for potent inhibition of arginase,
as N
δ-hydroxy-l-ornithine, which has one -CH2 group less than N
ε-hydroxy-l-lysine, exhibited a 37-fold higher Ki value than N
ε-hydroxy-l-lysine. Based on these results, a model for the interaction of N
ω-hydroxyamino-l-α-amino acids with the arginase active site is proposed. This model involves the binding of the N-OH group of the inhibitors
to the arginase Mn(II) center and suggests that N
ε-hydroxy-l-lysine is a good transition state analog of arginase. 相似文献
42.
Nicolas Bouquin Mao X. Chen Sunghoon Kim Françoise Vannier Sylvie Bernard I. Barry Holland Simone J. Séror 《Molecular microbiology》1996,20(4):853-865
We previously described a mutation feeB1 conferring a temperature-sensitive filamentation phenotype and resistance to the calmodulin inhibitor 48/80 in Escherichia coli, which constitutes a single base change in the acceptor stem of the rare tRNA3Leu recognizing CUA codons. We now describe a second mutant, feeA1, unlinked to feeB, but displaying a similar phenotype, 48/80 resistance and a reduced growth rate at the permissive temperature, 30°C, and temperature-sensitive, forming short filaments at 42°C. In the feeA mutant, tRNA3Leu expression (but not that of tRNA1Leu) was reduced approximately fivefold relative to the wild type. We previously showed that the synthesis of β-galactosidase, which unusually requires the translation of 6-CUA codons, was substantially reduced, particularly at 42°C, in feeB mutants. The feeA mutant also shows drastically reduced synthesis of β-galactosidase at the non-permissive temperature and reduced levels even at the permissive temperature. We also show that increased copy numbers of the abundant tRNA1Leu, which can also read CUA codons at low efficiency, suppressed the effects of feeA1 under some conditions, providing further evidence that the mutant was deficient in CUA translation. This, and the previous study, demonstrates that mutations which either reduce the activity of tRNA3Leu or the cellular amount of tRNA3Leu confer resistance to the drug 48/80, with concomitant inhibition of cell division at 42°C. 相似文献
43.
Sophie Lepage Bernard Lakaye Moreno Galleni Iris Thamm Michel Crine Sylvie Groslambert Jean-Marie Frère 《Molecular microbiology》1995,16(2):365-372
With the help of a new highly sensitive method allowing the quantification of free penicillin-binding proteins (PBPs) and of an integrated mathematical model, the progressive saturation of PBP1 by various β-lactam antibiotics in growing cells of Bacillus licheniformis was studied. Although the results confirmed PBP1 as a major lethal target for these compounds, they also underlined several weaknesses in our present understanding of this phenomenon. In growing cells, but not in resting cells, the penicillin target(s) appeared to be somewhat protected from the action of the inactivators. In vitro experiments indicated that amino acids, peptides and depsipeptides mimicking the peptide moiety of the nascent peptidoglycan significantly interfered with the acylation of PBP1 by the antibiotics. In addition, the level of PBP1 saturation at antibiotic concentrations corresponding to the minimum inhibitory concentrations was not constant, suggesting that additional, presently undiscovered, factors might be necessary to account for the experimental observations. 相似文献
44.
Catherine Iehl Sylvie Dlos Olivier Guirou Rothwell Tate Jean-Pierre Raynaud Pierre-Marie Martin 《The Journal of steroid biochemistry and molecular biology》1995,54(5-6)
The present study describes the independent expression of the type 1 and 2 isoforms of human 5α-reductase in the baculovirus-directed insect cell expression system and the selectivity of their inhibition. The catalytic properties and kinetic parameters of the recombinant isozymes were consistent with published data. The type 1 isoform displayed a neutral (range 6–8) pH optimum and the type 2 isoform an acidic (5–6) pH optimum. The type 2 isoform had higher affinity for testosterone than did the type 1 isoform (Km = 0.5 and 2.9 μM, respectively). Finasteride and turosteride were selective inhibitors of the type 2 isoform (Ki (type 2) = 7.3 and 21.7 nM compared to Ki (type 1) = 108 and 330 nM, respectively). 4-MA and the lipido-sterol extract of Serenoa repens (LSESr) markedly inhibited both isozymes (Ki (type 1) = 8.4 nM and 7.2 μg/ml, respectively; Ki (type 2) = 7.4 nM and 4.9 μg/ml, respectively). The three azasteroids were competitive inhibitors vs substrate, whereas LSESr displayed non-competitive inhibition of the type 1 isozyme and uncompetitive inhibition of the type 2 isozyme. These observations suggest that the lipid component of LSESr might be responsible for its inhibitory effect by modulating the membrane environment of 5α-reductase. Partially purified recombinant 5α-reductase type 1 activity was preserved by the presence of lipids indicating that lipids can exert either stimulatory or inhibitory effects on human 5α-reductase. 相似文献
45.
Cells of Escherichia coli induced for l-tryptophan synthase [l-serine hydro-lyase (adding indole-glycerol-phosphate), EC 4.2.1.20] have been assayed in DMF and DMSO aqueous solvents as reaction medium. Up to 20% DMF/water, cells retained 90% of their tryptophan synthase activity. Concentrations of 20 mM indole, which did not inhibit this reactivity, could be reached with 5% DMF/water. Four matrices were compared for cell immobilization: polyacrylamide, foam particles of bovine seum albumin, alginate and κ-carrageenan. The best activity was retained with the latter matrix, and the preparations thus obtained allowed high productivity of l-tryptophan. Various systems of production of l-tryptophan with κ-carrageenan and DMF/water were studied. 相似文献
46.
Summary
Claviceps purpurea strain 129 was cultivated under submerged conditions in a sucrose-citrate medium containing high (36.8 mM) or low (1.84 mM) KH2PO4 concentrations. The permeabilized cells and culture supernatants contained alkaline and acid phosphatases. In the medium containing a high phosphate concentration, the synthesis of extracellular phosphatases was repressed, but that of cellular phosphatases was not. Extracellular phosphatases, especially alkaline phosphatases, were derepressed by transferring the mycelium into a phosphate-free medium. This derepression was inhibited by cycloheximide. In the presence of cycloheximide, the activities of the cellular phosphatases decreased markedly, indicating turnover of these enzymes. The cellular acid phosphatase was inhibited by phosphate (0.025 M–0.1 M) and NaF (0.01 M) while the cellular alkaline phosphatase was only inhibited by phosphate. Both cellular and extracellular alkaline phosphatases were more sensitive to repression by phosphate than the acid phosphatases. The alkaloid synthesizing enzymes were: a) present in mycelia grown in high levels of phosphate and b) activated by decreasing the intracellular phosphate level. 相似文献
47.
Debaryomyces phaffii inulinase was immobilized by adsorption on DEAE-cellulose. The immobilization caused a drop in optimum pH, a slight increase in optimum temperature and an important increase in the thermal stability of the system. The activity yield of immobilized inulinase was 75%.A continuous reactor operation was carried out. The utilization of this system permited the production of fructose syrup from inulin. 相似文献
48.
Alfred Berteloot Christiane Malo Sylvie Breton Michel Brunette 《The Journal of membrane biology》1991,122(2):111-125
Summary Kinetic data in (brush-border) membrane vesicles which rely on the validity of the initial rate assumption for their interpretation and depend on tracer flux studies using the rapid filtration technique for their experimental measurement have been limited to some extent by the absence of techniques that would allow for real-time data analysis. In this paper, we report on our successful design of a fast sampling, rapid filtration apparatus (FSRFA) which seems to fill up this technical gap since showing the following characteristics: (i) rapid injection (5 msec) and mixing (less than 100 msec) of small amounts of vesicles (10–40 l) with an incubation medium (0.2–1.0 ml); (ii) fast (20 to 80 msec depending on the sample volume) and multiple (up to 18 samples at a maximal rate of 4/sec) sampling of the uptake mixture followed by rapid quenching in the stop solution (approximately 5 msec) according to a predetermined time schedule (any time combination from 0.25 to 9999 sec); and (iii) fast, automated, and sampling-synchronized filtration and washings of the quenched uptake medium (only 15–20 sec are necessary for the first filtration followed by two washings and extra filtrations). As demonstrated using adult human jejunal brush-border membrane vesicles and Na+-d-glucose cotransport as models, the FSRFA accurately reproduces the manual aspects of the rapid filtration technique while allowing for very precise initial rate determinations. Moreover, the FSRFA has also been designed to provide as much versatility as possible and, in its present version, allows for a very precise control of the incubation temperature and also permits a few efflux protocols to be performed. Finally, its modular design, which separates the fast sampling unit from the rapid filtration device, should help in extending its use to fields other than transport measurement. 相似文献
49.
Armelle Baeza-Squiban Sylvie Romet Anne Moreau Francelyne Marano 《In vitro cellular & developmental biology. Animal》1991,27(6):453-460
Summary Primary cultures of rabbit tracheal cells were obtained as outgrowths from explants of tracheal mucosa. A 30% collagen substratum
containing serum and minimal essential medium was required for obtaining an outgrowth of epithelial cells keeping their differentiated
characteristics. The tracheal epithelial cells obtained near the explant in the first days of culture presented morphologic
similarities with normal tracheal epithelium. Cultures contained basal cells and epithelial polarized cells that exhibited
apical tight junctions and desmosomes. Ciliated cells stayed functional during all time culture. Their number slightly increased
at the beginning of the culture and then stayed constant when the total number of cells increased. Development of the outgrowth
was rapid and significant inasmuch as the outgrowth surface reached 30 times that of the explant after less than 8 days. This
was linked to cellular proliferation, as demonstrated by the incorporation of bromodeoxyuridine (BrdU) in phase-S nuclei and
the revelation of BrdU using an immunofluorescence technique. The epithelial nature of the outgrowth cells and the absence
of contamination with fibroblasts were established by positive staining with anti-keratin antibody and by negative staining
with anti-vimentin antibody, respectively.
This work was supported by DRET and by CIFRE grant awarded to S. R. 相似文献
50.
Sylvie Tutois Josselyne Salaun Marie-Geneviève Mattei Jean-Louis Guénet 《Mammalian genome》1991,1(3):184-190
Transgenic mice generated with different DNA sequences were surveyed for possible homozygous mutant phenotypes. We found an embryonic lethal mutation in the transgenic mouse strain (MT-MYC12.4) containing the human c-myc gene. Embryos homozygous for the transgene die shortly after implantation. The strain MT-MYC12.4 carries approximately 50 tandem copies of the recombinant plasmid sequence. The 3 flanking sequence has been cloned and analyzed. It contains a unique sequence that has been conserved during evolution and maps to Chromosome (Chr) 9. This mutant has been designated Tg 9 (HSA-MYC). 相似文献