全文获取类型
收费全文 | 4074篇 |
免费 | 202篇 |
国内免费 | 190篇 |
专业分类
4466篇 |
出版年
2024年 | 7篇 |
2023年 | 63篇 |
2022年 | 100篇 |
2021年 | 127篇 |
2020年 | 124篇 |
2019年 | 143篇 |
2018年 | 142篇 |
2017年 | 105篇 |
2016年 | 105篇 |
2015年 | 146篇 |
2014年 | 248篇 |
2013年 | 302篇 |
2012年 | 197篇 |
2011年 | 191篇 |
2010年 | 152篇 |
2009年 | 215篇 |
2008年 | 234篇 |
2007年 | 248篇 |
2006年 | 231篇 |
2005年 | 201篇 |
2004年 | 177篇 |
2003年 | 166篇 |
2002年 | 138篇 |
2001年 | 99篇 |
2000年 | 79篇 |
1999年 | 56篇 |
1998年 | 65篇 |
1997年 | 68篇 |
1996年 | 49篇 |
1995年 | 35篇 |
1994年 | 34篇 |
1993年 | 42篇 |
1992年 | 26篇 |
1991年 | 21篇 |
1990年 | 20篇 |
1989年 | 14篇 |
1988年 | 27篇 |
1987年 | 7篇 |
1986年 | 7篇 |
1985年 | 5篇 |
1984年 | 9篇 |
1983年 | 12篇 |
1982年 | 8篇 |
1981年 | 11篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1976年 | 2篇 |
1975年 | 1篇 |
排序方式: 共有4466条查询结果,搜索用时 0 毫秒
1.
《Journal of molecular biology》2021,433(4):166764
Apical sodium-dependent bile acid transporter (ASBT) catalyses uphill transport of bile acids using the electrochemical gradient of Na+ as the driving force. The crystal structures of two bacterial homologues ASBTNM and ASBTYf have previously been determined, with the former showing an inward-facing conformation, and the latter adopting an outward-facing conformation accomplished by the substitution of the critical Na+-binding residue glutamate-254 with an alanine residue. While the two crystal structures suggested an elevator-like movement to afford alternating access to the substrate binding site, the mechanistic role of Na+ and substrate in the conformational isomerization remains unclear. In this study, we utilized site-directed alkylation monitored by in-gel fluorescence (SDAF) to probe the solvent accessibility of the residues lining the substrate permeation pathway of ASBTNM under different Na+ and substrate conditions, and interpreted the conformational states inferred from the crystal structures. Unexpectedly, the crosslinking experiments demonstrated that ASBTNM is a monomer protein, unlike the other elevator-type transporters, usually forming a homodimer or a homotrimer. The conformational dynamics observed by the biochemical experiments were further validated using DEER measuring the distance between the spin-labelled pairs. Our results revealed that Na+ ions shift the conformational equilibrium of ASBTNM toward the inward-facing state thereby facilitating cytoplasmic uptake of substrate. The current findings provide a novel perspective on the conformational equilibrium of secondary active transporters. 相似文献
2.
3.
Summary The influence of total nitrification to nitrate or partial nitrification to nitrite on the soil organic nitrogen status was examined. NH
4
+
–15N was added to the soil in the absence and the presence of NaClO3, respectively nitrapyrin. The first chemical inhibits only nitrate formation, the second inhibits total nitrification. The accumulation of nitrite nitrogen in the soil at levels up to 5 mg kg–1 increased the loss of nitrogen. Yet, it did not increase the binding of mineral nitrogen into soil organic matter, relative to the control soil. The data suggest that the biochemistry of the nitrite formation process, rather than the levels of nitrite ions formed, are of primary importance in the role of nitrification mediated nitrosation of soil organic matter. 相似文献
4.
Makoto Tajima Nobuko Sekiguchi Masao Fujimaki 《Bioscience, biotechnology, and biochemistry》2013,77(2):319-320
High phosphate accumulating bacteria were isolated by autoradiography. One isoate, Arthrobacter globiformis PAB-6 accumulated phosphate intracellularly at 20% of dry cell mass in a simple synthetic medium. This amount was 3~7 times higher than type cultures examined. Almost no phosphate was released into the medium after cessation of growth. Fifty percent of total intracellular phosphate was fractionated as nucleic acids, while 20% each was recovered from cold PCA soluble fractions and polyphosphate fractions. The large content of nucleic acids in this bacterium appeared due to increased RNA content, specifically 4 S RNA fraction. 相似文献
5.
Meta‐analyses evaluating the association between the serotonin transporter polymorphism (5‐HTTLPR) with neuroticism and depression diagnosis as phenotypes have been inconclusive. We examined a gene–environment interaction on a cognitive vulnerability marker of depression, cognitive reactivity (CR) to sad mood. A total of 250 university students of European ancestry were genotyped for the 5‐HTTLPR, including SNP rs25531, a polymorphism of the long allele. Association analysis was performed for neuroticism, CR and depression diagnosis (using a self‐report measure). As an environmental pathogen, self‐reported history of childhood emotional abuse was measured because of its strong relationship with depression. Participants with the homozygous low expressing genotype had high CR if they had experienced childhood emotional maltreatment but low CR if they did not have such experience. This interaction was strongest on the Rumination subscale of the CR measure. The interaction was not significant with neuroticism or depression diagnosis as outcome measures. Our results show that 5‐HTTLPR is related to cognitive vulnerability to depression. Our findings provide evidence for a differential susceptibility genotype rather than a vulnerability genotype, possibly because of the relatively low levels of abuse in our sample. The selection of phenotype and environmental contributor is pivotal in investigating gene–environment interactions in psychiatric disorders. 相似文献
6.
Michel R. Pâquet Robert J. Romanek Robert J. Sargeant 《Molecular and cellular biochemistry》1992,109(2):149-155
Summary In rat adipocytes, the insulin stimulation of the rate of glucose uptake is due, at least partially, to the recruitment of glucose transporter proteins from an intracellular compartment to the plasma membrane.Vanadate is a known insulin mimetic agent and causes an increase in the rate of glucose transport in rat adipocytes similar to that seen with insulin. The objective of the present study was to determine whether vanadate exerts its effect through the recruitment of glucose transporters to the plasma membrane.We report that under conditions where vanadate stimulates the rate of 2-deoxyglucose uptake to the same extent as insulin, the concentration of GLUT-4 in the plasma membrane was increased similarly by both insulin and vanadate, and its concentration was decreased in the low density microsomal fraction. These results suggest that vanadate induces the recruitment of GLUT-4 to the plasma membrane. The effects of vanadate and insulin on the stimulation of 2-deoxyglucose uptake and recruitment of GLUT-4 were not additive.This is the first report of an effect of vanadate on the intracellular distribution of the glucose transporter. 相似文献
7.
The effects of mineral salts constituting water hardness on fecundity ofDaphnia magna were assessed. Of the salts tested, increased concentrations of NaHCO3 and MgSO4 had no effect on fecundity, CaSO4 significantly increased fecundity, and KCl significantly reduced fecundity. The number of offspring produced per daphnid
was correlative to the CaSO4 concentration at CaSO4 concentrations between 91 and 2100 mg/ℓ. The effects of CaSO4 on daphnid fecundity could influence the interpretive outcome of industrial wastewater toxicity tests using this species
when the waste and dilution waters contain different concentrations of CaSO4. It is recommended that when performing these tests, dilution water be sampled at the intake site of the industry's water
source, thus assuring initial comparability of the waste and dilution waters. The CaSO4 content of the water prior to and after industrial use should be determined to identify any alterations of CaSO4 concentration during use. Identification of CaSO4 concentration differences can aid in the interpretation of effects associated with the wastewater. 相似文献
8.
David G. Griffiths Michael D. Partis Perry Churchill Stephen C. Brenner Sidney Fleischer Roger J. Moore R. Brian Beechey 《Journal of bioenergetics and biomembranes》1990,22(5):691-707
A series of amphiphilic polymethylenecarboxymaleimides has been synthesized for use as sulfhydryl reagents applicable to membrane proteins. Physical properties of the compounds which are relevant to their proposed mode of action have been determined. By comparing rates of reaction in aqueous and aprotic solvents, the compounds have been shown to react exclusively with the thiolate ion. The effects of the reagents on three membrane-associated proteins are reported, and in two cases a comparative study has been made of the effects on the proteins in the absence of membranes. A mechanism is proposed whereby the reagents are anchored at the lipid/water interface by the negatively charged carboxyl group, thus siting the reactive maleimide in a plane whose depth is defined by the length of the reagent. Supporting evidence for this model is provided by the inability of the reagents to traverse membranes, and variation of their inhibitory potency with chain length when the proteins are embedded in the membrane, but not when extracted into solution. As examples of general use of the reagents to probe sulfhydryl groups in membrane proteins, the reagents have been used to (a) determine the depths in the membrane at which two populations of sulfhydryl groups occur in the mitochondrial phosphate transporter; (b) locate a single sulfhydryl associated with the active site ofD--hydroxybutyrate dehydrogenase in the inner mitochondrial membrane; (c) examine sulfhydryl groups in theD-3-glyceraldehyde phosphate dehydrogenase associated with the human red blood cell membrane. 相似文献
9.
Nicotine Effects on Dopamine Clearance in Rat Nucleus Accumbens 总被引:2,自引:0,他引:2
Abstract: In vivo voltammetry was used to measure the clearance of exogenously applied dopamine (DA) in the nucleus accumbens following acute systemic nicotine administration in urethane-anesthetized rats. The IVEC-5 system was used for continuous in vivo electrochemical measurements. A finite amount of DA was pressure-ejected (25–100 nl, 200 µ M barrel concentration) at 5-min intervals from micropipettes (tip diameter, 10–15 µm) positioned 250 ± 50 µm from the recording electrode. The peak DA concentration after each DA ejection was significantly decreased in rats following nicotine, but not in rats given saline. In addition, when mecamylamine was administered 20 min before nicotine it clearly antagonized nicotine effects. These results suggest that nicotine may actually facilitate DA transporter systems within the nucleus accumbens. 相似文献
10.
Ahmed S. Rahman Mieko Kimura Katsuhiko Yokoi Tanvir-E Naher Yoshinori Itokawa 《Biological trace element research》1996,53(1-3):57-64
Three groups of rats were fed two types of synthetic diets for 52 d. The—A group was allowed free access to a vitamin A-deficient
diet and showed classical signs of vitamin A deficiency. The brain was the only organ in our experiment where no significant
weight difference was present among the three groups. In the brain, calcium concentration was significantly higher in the—A
group when compared with the PF (Pair-fed; allowed restricted amount of control diet) and +A groups (allowed free access to
control diet). In the tibia, calcium and magnesium concentrations were significantly lower in the—A group when compared with
other two groups. Excessive accumulation of calcium in brain and apparently similar unbalance in bone, mineral concentration
were observed in central nervous system (CNS) degenerative diseases. Our results suggest that abnormal metabolism of calcium
and magnesium in some tissues and excessive accumulation of calcium in brain may be responsible for the development of neurological
disorders in vitamin A-deficient rats. 相似文献