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1.
Catherine Bonaïti-Pellié Françoise Clerget-Darpoux Marie-Claude Babron 《Human genetics》1990,86(2):203-208
Summary Although the retinoblastoma gene has been isolated and sequenced, the difference in penetrance and expressivity among families has not yet been fully explained. Balanced chromosomal insertion involving the 13q14 regions has been shown to account for some families with several unaffected carriers. Since there could be cases with karyotypically undetectable insertions, we tested whether this mechanism was general enough to explain the whole difference in expressivity among families. Using 166 pedigrees, reported in nine series available in the literature (including our own), we conclude that balanced insertion cannot entirely explain the familial data, even if we allow for a reduced viability of unbalanced gametes. Other mechanisms are proposed and discussed in this paper. 相似文献
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Marie-Claude Pepin Serge Beaulieu Nicholas Barden 《Cellular and molecular neurobiology》1990,10(2):227-235
1. Differential regulation, by dexamethasone, of glucocorticoid receptor gene expression was studied in three different neuronal cultures derived from hypothalamus amygdala, and cerebral cortex. 2. Cellular glucocorticoid receptor (GR) mRNA concentration was measured by hybridization using a 32P-labeled RNA probe complementary to a 2.2-kb fragment of the glucocorticoid receptor mRNA. Changes in the amount of GR mRNA were evaluated in relation to the content of beta-actin mRNA. 3. In cells derived from either hypothalamus or cerebral cortex, we observed a complex pattern of GR mRNA concentrations which were characterized by cyclic variations of GR mRNA content during continuous treatment with dexamethasone for up to 72 hr. 4. In contrast to cells derived from the hypothalamus where a persistent 30-40% reduction in GR mRNA levels was seen for up to a least 72 hr, we observed, in cells derived from the cerebral cortex, a sustained increased (1.4-fold) of the GR mRNA at this same time interval. 相似文献
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Jan Hendrickx Paul Coucke Marie-Claude Hors-Cayla G. Peter A. Smit Yoon S. Shin Johann Deutsch Jan Smeitink Ruud Berger Philip Lee John Fernandes Patrick J. Willems 《Genomics》1994,21(3)
We describe here a new type of X-linked liver glycogen storage disease. The main symptoms include liver enlargement and growth retardation. The clinical and biochemical abnormalities of this glycogenosis are similar to those of classical X-linked liver glycogenosis due to phosphorylase kinase deficiency (XLG). However, in contrast to patients with XLG, the patients described here have no reduced phosphorylase kinase activity in erythrocytes and leukocytes, and no enzyme deficiency could be found. Linkage analysis of four families with this X-linked type of liver glycogenosis assigned the disease gene to Xp22. Lod scores obtained with the markers DXS987, DXS207, and DXS999 were 3.97, 2.71, and 2.40, respectively, all at 0% recombination. Multipoint linkage analysis localized the disease gene between DXS143 and DXS989 with a maximum lod score of 4.70 at θ = 0, relative to DXS987. As both the classical XLG gene and the liver α-subunit of PHK (PHKA2) are also located in Xp22, this variant type of XLG may be allelic to classical XLG, and both diseases may be caused by mutations in PHKA2. Therefore, we propose to classify XLG as XLG type I (the classical type of XLG) and XLG type II (the variant type of XLG). 相似文献
6.
Fabrice Cornille Loïc Martin Christine Lenoir Didier Cussac Bernard P. Roques Marie-Claude Fournié-Zaluski 《Letters in Peptide Science》1997,4(4-6):207-212
The light chain of tetanus neurotoxin (TeNT L chain)has been shown to be endowed with zinc endopeptidaseactivity, selectively directed towards theGln76–Phe77 bond of synaptobrevin, avesicle-associated membrane protein criticallyinvolved in neuroexocytosis. In previous reports,truncations at the NH2- and COOH-terminus ofsynaptobrevin have shown that the sequence 39–88 ofsynaptobrevin is the minimum substrate of TeNT,suggesting either the requirement of a well-definedthree-dimensional structure of synaptobrevin or a rolein the mechanism of substrate hydrolysis for residuesdistal from the cleavage site. In this study, theaddition of NH2- and COOH-terminal peptides ofsynaptobrevin, S 27–55 (S1) and S 82–93(S2), to the synaptobrevin fragment S 56–81allowed the cleavage of this latter peptide by TeNT tooccur. This appears to result from an activationprocess mediated by the simultaneous binding ofS1 and S2 with complementary sites presenton TeNT as shown by surface plasmon resonanceexperiments. All these results favor anexosite-controlled hydrolysis of synaptobrevin by TeNTprobably involving a conformational change of thetoxin. This could account for the high degree ofsubstrate specificity of TeNT and, probably, botulinumneurotoxins. 相似文献
7.
Robert Barouki Marie-Noële Chobert Marie-Claude Billon Joëlle Finidori Rosine Tsapis Jacques Hanoune 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》1982,721(1):11-21
γ-Glutamyltransferase activity was detected in the plasma membrane of the highly differentiated hepatoma cell line Fao, (0.93 mU/mg cell protein). Dexamethasone (1 μM) provoked a 2–3-fold increase in the activity of the enzyme in the presence of fetal calf serum. Maximal induction occurred 48–72 h after addition of the glucocorticoid to the cell culture medium. The hormonal specificity was demonstrated by the relative potencies of several glucocorticoids and sex steroids: hydrocortisone and corticosterone increased γ-glutamyltransferase activity while tetrahydrocorticosterone and all sex steroids tested were ineffective. The effect of dexamethasone on γ-glutamyltransferase activity was specific since the activities of several other plasma membrane enzymes were not modified. The mechanism of the dexamethasone-induced increase in γ-glutamyltransferase activity was neither by modification of the affinity of the enzyme for its substrates nor by alteration of the subcellular distribution of the enzyme. This increase was prevented by cycloheximide and actinomycin D. The data presented are consistent with a specific glucocorticoid receptor-mediated induction of γ-glutamyltransferase activity in Fao cells. The kinetic parameters of the induction process by glucocorticoids are very similar to those found in adult rat liver. These results suggest that the Fao cell line is a very convenient system for the study of the molecular mechanisms of glucocorticoid effects on differentiated cells. 相似文献
8.
NARC-1/PCSK9 and its natural mutants: zymogen cleavage and effects on the low density lipoprotein (LDL) receptor and LDL cholesterol 总被引:1,自引:0,他引:1
Benjannet S Rhainds D Essalmani R Mayne J Wickham L Jin W Asselin MC Hamelin J Varret M Allard D Trillard M Abifadel M Tebon A Attie AD Rader DJ Boileau C Brissette L Chrétien M Prat A Seidah NG 《The Journal of biological chemistry》2004,279(47):48865-48875
The discovery of autosomal dominant hypercholesterolemic patients with mutations in the PCSK9 gene, encoding the proprotein convertase NARC-1, resulting in the missense mutations suggested a role in low density lipoprotein (LDL) metabolism. We show that the endoplasmic reticulum-localized proNARC-1 to NARC-1 zymogen conversion is Ca2+-independent and that within the zymogen autocatalytic processing site SSVFAQ [downward arrow]SIP Val at P4 and Pro at P3' are critical. The S127R and D374Y mutations result in approximately 50-60% and > or =98% decrease in zymogen processing, respectively. In contrast, the double [D374Y + N157K], F216L, and R218S natural mutants resulted in normal zymogen processing. The cell surface LDL receptor (LDLR) levels are reduced by 35% in lymphoblasts of S127R patients. The LDLR levels are also reduced in stable HepG2 cells overexpressing NARC-1 or its natural mutant S127R, and this reduction is abrogated in the presence of 5 mm ammonium chloride, suggesting that overexpression of NARC-1 increases the turnover rate of the LDLR. Adenoviral expression of wild type human NARC-1 in mice resulted in a maximal approximately 9-fold increase in circulating LDL cholesterol, while in LDLR-/- mice a delayed approximately 2-fold increase in LDL cholesterol was observed. In conclusion, NARC-1 seems to affect both the level of LDLR and that of circulating apoB-containing lipoproteins in an LDLR-dependent and -independent fashion. 相似文献
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10.
Alexandre Sasseville Dalila Benhaberou-Brun Charlotte Fontaine Marie-Claude Charon 《Chronobiology international》2013,30(5):913-925
Night shiftworkers often complain of disturbed sleep during the day. This could be partly caused by morning sunlight exposure during the commute home, which tends to maintain the circadian clock on a daytime rhythm. The circadian clock is most sensitive to the blue portion of the visible spectrum, so our aim was to determine if blocking short wavelengths of light below 540 nm could improve daytime sleep quality and nighttime vigilance of night shiftworkers. Eight permanent night shiftworkers (32–56 yrs of age) of Quebec City's Canada Post distribution center were evaluated during summertime, and twenty others (24–55 yrs of age) during fall and winter. Timing, efficacy, and fragmentation of daytime sleep were analyzed over four weeks by a wrist activity monitor, and subjective vigilance was additionally assessed at the end of the night shift in the fall–winter group. The first two weeks served as baseline and the remaining two as experimental weeks when workers had to wear blue-blockers glasses, either just before leaving the workplace at the end of their shift (summer group) or 2 h before the end of the night shift (fall–winter group). They all had to wear the glasses when outside during the day until 16:00 h. When wearing the glasses, workers slept, on average ±SD, 32±29 and 34±60 more min/day, increased their sleep efficacy by 1.95±2.17% and 4.56±6.1%, and lowered their sleep fragmentation by 1.74±1.36% and 4.22±9.16% in the summer and fall–winter group, respectively. Subjective vigilance also generally improved on Fridays in the fall–winter group. Blue-blockers seem to improve daytime sleep of permanent night-shift workers. 相似文献