全文获取类型
收费全文 | 18918篇 |
免费 | 1053篇 |
国内免费 | 975篇 |
出版年
2023年 | 245篇 |
2022年 | 388篇 |
2021年 | 507篇 |
2020年 | 504篇 |
2019年 | 735篇 |
2018年 | 650篇 |
2017年 | 409篇 |
2016年 | 427篇 |
2015年 | 571篇 |
2014年 | 1090篇 |
2013年 | 1364篇 |
2012年 | 824篇 |
2011年 | 1164篇 |
2010年 | 835篇 |
2009年 | 851篇 |
2008年 | 938篇 |
2007年 | 938篇 |
2006年 | 831篇 |
2005年 | 790篇 |
2004年 | 739篇 |
2003年 | 659篇 |
2002年 | 562篇 |
2001年 | 380篇 |
2000年 | 371篇 |
1999年 | 340篇 |
1998年 | 312篇 |
1997年 | 259篇 |
1996年 | 280篇 |
1995年 | 252篇 |
1994年 | 288篇 |
1993年 | 222篇 |
1992年 | 226篇 |
1991年 | 209篇 |
1990年 | 139篇 |
1989年 | 141篇 |
1988年 | 119篇 |
1987年 | 110篇 |
1986年 | 100篇 |
1985年 | 165篇 |
1984年 | 155篇 |
1983年 | 93篇 |
1982年 | 127篇 |
1981年 | 127篇 |
1980年 | 109篇 |
1979年 | 88篇 |
1978年 | 76篇 |
1977年 | 54篇 |
1976年 | 60篇 |
1975年 | 31篇 |
1974年 | 30篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
81.
M. Wachsman L. Aurelian J. C. R. Hunter M. E. Perkus E. Paoletti 《Bioscience reports》1988,8(4):323-334
We studied the effect of the temporal regulation of herpes simplex virus (HSV) type 1 glycoprotein D (gD-1) expression in Ia+ epidermal cells (EC) and macrophages on virus specific immunity and protection from HSV-2 challenge. gD-1 was expressed on the surface of cells infected with a vaccinia recombinant containing gD-1 under the control of an early vaccinia virus promoter (VP176). It was not expressed in cells infected with a recombinant (VP254) in which gD-1 is controlled by a late vaccinia virus promoter. BALB/c mice immunized with both recombinants seroconverted to HSV-2 as determined by neutralization. However, HSV specific delayed type hypersensitivity (DTH) responses were significantly (p<0.025) higher in VP176 than VP254 immunized animals. Both VP176 and VP254 immunized mice were protected from severe neurological disease due to HSV-2 challenge at 14 days post immunization, but long term protection was observed only in VP176 immunized mice. 相似文献
82.
UV-visible and 13C NMR measurements described in the literature and our 31P NMR measurements support the following mechanism of proton transfer reactions in aqueous solutions of pyridoxamine phosphate: Only the tautomeric equilibrium between neutral form, A
N, and zwitterion, A
Z, which is analogous to the tautomeric equilibrium of 3-hydroxypyridine in aqueous solution, is important, and that equilibrium does not change upon the dissociation of the second phosphate proton. With these simplifying assumption, we have simulated the relaxation spectrum of the proton transfer reactions of pyridoxamine phosphate in water using parameters from analogous reactions and compared it with our ultrasound and temperature jump measurements. We have found that the relaxation process measured by the temperature jump experiment is mainly caused by the overall reaction A
N=A
Z (or A
N
-
=A
Z
-
) and the ultrasound absorption at the isoelectric point between pK2 and pK3 is mainly caused by the overall reaction
. 相似文献
83.
Formation of the Neurotransmitter Glycine from the Anticonvulsant Milacemide Is Mediated by Brain Monoamine Oxidase B 总被引:5,自引:1,他引:4
Philippe Janssens de Varebeke Robert Cavalier Michèle David-Remacle Moussa B. H. Youdim 《Journal of neurochemistry》1988,50(4):1011-1016
Milacemide (2-n-pentylaminoacetamide) is a secondary monoamine that in the brain is converted to glycinamide and glycine. This oxidative reaction was suspected to involve the reaction of monoamine oxidase (MAO). Using mitochondrial preparations from tissues that contain MAO-A and -B (rat brain and liver), MAO-A (human placenta), and MAO-B (human platelet and bovine adrenal chromaffin cell), it has been established that mitochondria containing MAO-B rather than MAO-A oxidize (H2O2 production and glycinamide formation) milacemide. The apparent Km (30-90 microM) for milacemide oxidation by mitochondrial MAO-B preparations is significantly lower than that for milacemide oxidation by mitochondrial MAO-A (approximately 1,300 microM). In vitro MAO-B (l-deprenyl and AGN 1135) rather than MAO-A (clorgyline) selectively inhibited the oxidation of milacemide. These in vitro data are matched by ex vivo experiments where milacemide oxidation was compared to oxidation of serotonin (MAO-A) and beta-phenylethylamine (MAO-B) by brain mitochondria prepared from rats pretreated with clorgyline (0.5-10 mg/kg) and l-deprenyl (0.5-10 mg/kg). Furthermore, in vivo experiment demonstrated that l-deprenyl selectively increased the urinary excretion of [14C]milacemide and the total radioactivity with a concomitant decrease of [14C]glycinamide. Such changes were not observed after clorgyline treatment, but were evident only at doses beyond clorgyline selectivity. The present data therefore demonstrate that milacemide is a substrate for brain MAO-B, and its conversion to glycinamide, further transformed to the inhibitory neurotransmitter, glycine, mediated by this enzyme may contribute to its pharmacological activities. 相似文献
84.
Jean-Paul Kan Régis Steinberg Jérome Leclercq Paul Worms Kathleen Biziere 《Journal of neurochemistry》1988,50(4):1137-1144
In rodents, SR 95191 [3-(2-morpholinoethylamino)-4-cyano-6-phenylpyridazine] has been shown to be active in animal models of depression. The profile of activity of SR 95191 suggests that the compound is a selective and short-acting type A monoamine oxidase (MAO) inhibitor (MAOI) in vivo. In the present study, the interaction of SR 95191 with MAO-A and MAO-B activity was further examined in vivo and in vitro. In brain, liver, and duodenum of pretreated rats, SR 95191 selectively inhibited MAO-A (ED50 = 3-5 mg/kg, p.o.), whereas MAO-B was only weakly inhibited for doses as high as 300 mg/kg, p.o. In vivo, SR 95191 (1-100 mg/kg, p.o.) antagonized, in a dose-dependent fashion, the irreversible inhibition of brain and liver MAO-A induced by phenelzine. Finally, dopamine and 5-hydroxytryptamine depleted from their striatal stores by tetrabenazine were able to displace SR 95191 from the active site of MAO-A. However, ex vivo, kinetic studies showed that the inhibitory effect of SR 95191 (1-10 mg/kg) towards MAO-A was noncompetitive and was unchanged after dilution or dialysis. In vitro, the inhibition of brain MAO-A, but not MAO-B, by SR 95191 was time dependent, with a 19-fold decrease in the IC50 values being observed over a 30-min incubation period (140 to 7.5 microM). At this time, the SR 95191-induced inhibition of MAO-A was not removed by repeated washings. When the reaction was started by adding the homogenate without prior preincubation with SR 95191, the inhibition of brain MAO-A was fully competitive (Ki = 68 microM).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
85.
Inhibition by Cyclic AMP of Phorbol Ester-Potentiated Norepinephrine Release from Guinea Pig Brain Cortical Synaptosomes 总被引:8,自引:4,他引:4
Hisato Shuntoh Kohtaro Taniyama Hisashi Fukuzaki Chikako Tanaka 《Journal of neurochemistry》1988,51(5):1565-1572
The involvement of Ca2+/phospholipid-dependent protein kinase (protein kinase C, PKC) and cyclic AMP-dependent protein kinase in the K+-evoked release of norepinephrine (NE) was studied using guinea pig brain cortical synaptosomes preloaded with [3H]NE. 12-O-Tetradecanoylphorbol-13-acetate (TPA), a potent activator of PKC, enhanced the K+-evoked release of [3H]NE, in a concentration-dependent manner, but with no effect on the spontaneous outflow and uptake of [3H]NE in the synaptosomes. The apparent affinity of the evoked release for added calcium but not the maximally evoked release was increased by TPA (10(-7) M). Inhibitors of PKC, polymyxin B, and a more potent inhibitor, staurosporine, counteracted the TPA-induced potentiation of the evoked release. Both forskolin and dibutyryl cyclic AMP (DBcAMP) enhanced the evoked release, but reduced the TPA-potentiated NE release. A novel inhibitor of cyclic AMP-dependent protein kinase, KT5720, blocked both the forskolin-induced increase in the evoked release and its inhibition of TPA-induced potentiation in the evoked release, thereby suggesting that forskolin or DBcAMP counteracts the Ca2+-dependent release of NE by activating cyclic AMP-dependent protein kinase. These results suggest that the activation of PKC potentiates the evoked release of NE and that the activation of cyclic AMP-dependent protein kinase acts negatively on the PKC-activated exocytotic neurotransmitter release process in brain synaptosomes of the guinea pig. 相似文献
86.
Summary We found two types of hemoglobin, T and R, from the crab-eating macaque and compared those to A and Q previously reported. The 22 animals studied showed six different phenotypes, A, R, QA, QT, QAT, and QAR. Analysis of the complete amino acid sequences for the chains of hemoglobins Q, A, T, and R revealed that amino acids at four positions, 8, 55, 71, and 78 from the N-terminal, are variable. In the A chain, Thr, Val, Gly, and Gln occupy these positions, and in the Q chain the analogous amino acids are Thr, Val, Asp, and Gln, respectively. In the newly found T chain they are Thr, Val, Gly, and His; and in the R chain, they are Ser, Ile, Gly, and His, respectively. Two amino acids (8 Thr and 79 Gln) in A of the crab-eating macaque were found to be different from those in the chain of the Japanese macaque. 相似文献
87.
François Iborra Alain Raynal Michel Guerineau 《Molecular & general genetics : MGG》1988,213(1):150-154
Summary The relationship between the promoter length of the Kluyveromyces fragilis -glucosidase gene and the level of its expression in Saccharomyces cerevisiae was studied by gene fusion between deleted promoter fragments of various lengths and the promoterless -galactosidase gene of Escherichia coli. The removal of a region from position-425 to-232 led to a tenfold increase in the expression of the gene. The same results were obtained for the reconstructed -glucosidase gene with the same promoter length. It is likely that the deletion of this part of the promoter removes negative regulatory elements which are functional in Saccharomyces cerevisiae. This increase in activity is the main event which may explain the high increase in gene expression (60-fold) previously observed for an upstream deletion obtained during subcloning experiments of the -glucosidase gene. It is also shown that the expression of the gene greatly depends upon the nature of the recipient strain, the growth phase of the cell and that of the vector carrying it. 相似文献
88.
Victor Chude 《Plant and Soil》1988,112(2):293-295
The profile distribution of total and extractable B was determined in 16 Nigerian cacao-growing soil profiles formed from
different parent materials. Total B for all soils ranged from 8 to 54μgg−1 with a mean of 24μgg−1. The soils formed from sandstones in the rainforest zone contained higher amounts of total B than soils derived from basement
complex. Boron extractable in hot water, in 0.1% CaCl2, and in 1N NH4OAc varied from 0.13 to 1.38, 0.44 to 1.20 0.03 to 0.56μgg−1 respectively. The corresponding means were 0.66, 0.75 and 0.27μgg−1 B. Soils on metamorphic rocks gave the highest values. All extractable B values were related to organic matter while only
CaCl2-extractable B correlated with total B. Generally total and extractable B values were higher in the top soils than in the
subsoils. 相似文献
89.
90.