全文获取类型
收费全文 | 114208篇 |
免费 | 5440篇 |
国内免费 | 8663篇 |
出版年
2023年 | 1242篇 |
2022年 | 1861篇 |
2021年 | 2355篇 |
2020年 | 2526篇 |
2019年 | 4062篇 |
2018年 | 2967篇 |
2017年 | 2380篇 |
2016年 | 2826篇 |
2015年 | 3955篇 |
2014年 | 5644篇 |
2013年 | 7627篇 |
2012年 | 4734篇 |
2011年 | 6452篇 |
2010年 | 5482篇 |
2009年 | 5110篇 |
2008年 | 5296篇 |
2007年 | 5767篇 |
2006年 | 5227篇 |
2005年 | 4813篇 |
2004年 | 4226篇 |
2003年 | 3615篇 |
2002年 | 3017篇 |
2001年 | 2432篇 |
2000年 | 2094篇 |
1999年 | 2140篇 |
1998年 | 1930篇 |
1997年 | 1710篇 |
1996年 | 1619篇 |
1995年 | 1823篇 |
1994年 | 1735篇 |
1993年 | 1602篇 |
1992年 | 1601篇 |
1991年 | 1370篇 |
1990年 | 1220篇 |
1989年 | 1145篇 |
1988年 | 1106篇 |
1987年 | 1077篇 |
1986年 | 786篇 |
1985年 | 1228篇 |
1984年 | 1685篇 |
1983年 | 1175篇 |
1982年 | 1556篇 |
1981年 | 1137篇 |
1980年 | 1108篇 |
1979年 | 1017篇 |
1978年 | 625篇 |
1977年 | 512篇 |
1976年 | 419篇 |
1975年 | 290篇 |
1973年 | 293篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
1.
《Journal of molecular biology》2021,433(15):167097
DNA glycosylases remove damaged or modified nucleobases by cleaving the N-glycosyl bond and the correct nucleotide is restored through subsequent base excision repair. In addition to excising threatening lesions, DNA glycosylases contribute to epigenetic regulation by mediating DNA demethylation and perform other important functions. However, the catalytic mechanism remains poorly defined for many glycosylases, including MBD4 (methyl-CpG binding domain IV), a member of the helix-hairpin-helix (HhH) superfamily. MBD4 excises thymine from G·T mispairs, suppressing mutations caused by deamination of 5-methylcytosine, and it removes uracil and modified uracils (e.g., 5-hydroxymethyluracil) mispaired with guanine. To investigate the mechanism of MBD4 we solved high-resolution structures of enzyme-DNA complexes at three stages of catalysis. Using a non-cleavable substrate analog, 2′-deoxy-pseudouridine, we determined the first structure of an enzyme-substrate complex for wild-type MBD4, which confirms interactions that mediate lesion recognition and suggests that a catalytic Asp, highly conserved in HhH enzymes, binds the putative nucleophilic water molecule and stabilizes the transition state. Observation that mutating the Asp (to Gly) reduces activity by 2700-fold indicates an important role in catalysis, but probably not one as the nucleophile in a double-displacement reaction, as previously suggested. Consistent with direct-displacement hydrolysis, a structure of the enzyme-product complex indicates a reaction leading to inversion of configuration. A structure with DNA containing 1-azadeoxyribose models a potential oxacarbenium-ion intermediate and suggests the Asp could facilitate migration of the electrophile towards the nucleophilic water. Finally, the structures provide detailed snapshots of the HhH motif, informing how these ubiquitous metal-binding elements mediate DNA binding. 相似文献
2.
Gad Avigad Priscilla J. Bohrer 《Biochimica et Biophysica Acta (BBA)/General Subjects》1984,798(3):317-324
6-Phosphofructo-2-kinase (ATP: D-fructose-6-phosphate-2-phosphotransferase) and D-fructose-2,6-bisphosphatase activities have been found in extracts prepared from etiolated mung bean seedlings. The activity of 6-phosphofructo-2-kinase exhibits a sigmoidal shape in response to changes in concentrations of both substrates, D-fructose 6-phosphate and ATP (S0.5 values of 1.8 and 1.2 mM, respectively). Inorganic orthophosphate (Pi) has a strong stimulating effect on the 2-kinase activity (A0.5 at about 2 mM), moderately increasing the Vmax and modifying the response into hyperbolic curves with Km values of 0.4 and 0.2 mM for fructose 6-phosphate and ATP, respectively. 3-Phosphoglycerate (I0.5 about 0.15 mM) partially inhibited the kinase activity by counteracting the Pi activation. In contrast, the activity of D-fructose-2,6-bisphosphatase (Km 0.38 mM) is strongly inhibited by Pi (I0.5 0.8 mM) lowering its affinity to fructose-2,6-P2 (Km 1.4 mM). 3-Phosphoglycerate activites the enzyme (A0.5 at about 0.3 mM) without causing a significant change in its Km for fructose-2,6-P2. The activities of both of these enzymes in relationship to the metabolic role of D-fructose 2,6-bisphosphate in the germinating seed is discussed. 相似文献
3.
Abstract. Nutrient conservation in vegetation affects rates of litter decomposition and soil nutrient availability. Although resorption has been traditionally considered one of the most important plant strategies to conserve nutrients in temperate forests, long leaf life‐span and low nutrient requirements have been postulated as better indicators. We aimed at identifying nutrient conservation strategies within characteristic functional groups of NW Patagonian forests on Andisols. We analysed C‐, N‐, P‐, K‐ and lignin‐concentrations in mature and senescent leaves of ten native woody species within the functional groups: broad‐leaved deciduous species, broad‐leaved evergreens and conifers. We also examined mycorrhizal associations in all species. Nutrient concentration in mature leaves and N‐ resorption were higher in broad‐leaved deciduous species than in the other two functional groups. Conifers had low mature leaf nutrient concentrations, low N‐resorption and high lignin/N ratios in senescent leaves. P‐ and K‐resorptions did not differ among functional groups. Broad‐leaved evergreens exhibited a species‐dependent response. Nitrogen in mature leaves was positively correlated with both N resorption and soil N‐fertility. Despite the high P‐retention capacity of Andisols, N appeared to be the more limiting nutrient, with most species being proficient in resorbing N but not P. The presence of endomycorrhizae in all conifers and the broad‐leaved evergreen Maytenus boaria, ectomycorrhizae in all Nothofagus species (four deciduous, one evergreen), and cluster roots in the broad‐leaved evergreen Lomatia hirsuta, would be possibly explaining why P is less limiting than N in these forests. 相似文献
4.
The vitamin D binding protein (Gc) and posttransferrin-2 (Ptf-2) phenotypes have been determined in a number of Belgian cattle breeds. A very slow migrating variant of the Gc protein — Gc C — has been found in White and Red East Flemish breed. This variant was absent from the other breeds studied. This slow variant was identified as a vitamin D binding protein by autoradiography. The Gc C protein was shown to be controlled by a codominant autosomal allele Gc C at the Gclocus. The Gc C protein is probably identical with a fraction previously described in buffalo and an Italian cattle breed. The allele frequencies for the Gc and Pft-2 systems are reported for several Belgian breeds of cattle. 相似文献
5.
6.
Binding of the cationic tetra(tributylammoniomethyl)-substituted hydroxoaluminum phthalocyanine (AlPcN4) to bilayer lipid membranes was studied by fluorescence correlation spectroscopy (FCS) and intramembrane field compensation (IFC) methods. With neutral phosphatidylcholine membranes, AlPcN4 appeared to bind more effectively than the negatively charged tetrasulfonated aluminum phthalocyanine (AlPcS4), which was attributed to the enhancement of the coordination interaction of aluminum with the phosphate moiety of phosphatidylcholine by the electric field created by positively charged groups of AlPcN4. The inhibitory effect of fluoride ions on the membrane binding of both AlPcN4 and AlPcS4 supported the essential role of aluminum-phosphate coordination in the interaction of these phthalocyanines with phospholipids. The presence of negative or positive charges on the surface of lipid membranes modulated the binding of AlPcN4 and AlPcS4 in accord with the character (attraction or repulsion) of the electrostatic interaction, thus showing the significant contribution of the latter to the phthalocyanine adsorption on lipid bilayers. The data on the photodynamic activity of AlPcN4 and AlPcS4 as measured by sensitized photoinactivation of gramicidin channels in bilayer lipid membranes correlated well with the binding data obtained by FCS and IFC techniques. The reduced photodynamic activity of AlPcN4 with neutral membranes violating this correlation was attributed to the concentration quenching of singlet excited states as proved by the data on the AlPcN4 fluorescence quenching. 相似文献
7.
《Chronobiology international》2013,30(2):217-227
Although there are several reports on ultradian and circadian rhythms in newborns, we found only one report in which infradian periodicities are described for heart-rate measurements in the early stages of human development. Here, we report infradian rhythms in the monthly range in the sleep/wake cycle of four infants studied along 24 consecutive weeks. Our procedure was applied to sleep diary records from four healthy newborns. The data were arranged in binary time series representing sleep (?1) or wake (1) states. These time series were integrated in order to obtain the cumulative sleep/wake time. A measure of the sleep/wake ratio (SWR) was obtained by computing the average slope of the cumulative sleep/wake time. To extract periodicities we applied the Fourier periodogram to the temporal course of the SWR. We found a notorious difference in the SWR pattern among infants. In two infants the SWR showed a marked linear decay, spending more time asleep than awake, while in the two other infants oscillated near zero. We found robust oscillations in all children. In all cases the Fourier periodogram results present significant power in the infradian range. From these results, we suggest that sleep and wake durations are probably modulated by some internal stimuli. 相似文献
8.
9.
Puerto Rican populations of two species of sea anemones (Bunodosoma cavernata and B. granulifera) which had previously been considered one were assayed electrophoretically for enzymes encoded by 12 loci. The two species shared no common allozymes at 6 of the 12 loci. Genetic distance and identity values based on these allozymes were computed for the Puerto Rican populations and for B. cavernata from Florida and B. granulifera from Panama. The Puerto Rican populations of both species had much higher genetic identities for their geographically distant conspecifics than for each other. These results indicate that the two species are reproductively isolated and should be considered as separate valid species. Average heterozygosities are presented which are the first published for coelenterate species. 相似文献
10.
W.J. Malaisse F. Malaisse-Lagae A. Sener 《Biochimica et Biophysica Acta (BBA)/General Subjects》1984,797(2):194-202
1. Because L-asparagine augments insulin release evoked by L-leucine, the metabolism of these two amino acids was investigated in rat pancreatic islets. 2. L-Leucine inhibited the uptake and deamidation of L-asparagine, but failed to exert any obvious primary effect upon the further catabolism of aspartate derived from exogenous asparagine. 3. L-Asparagine augmented the oxidation of L-leucine, and effect possibly attributable to activaion of 2-ketoisocaproate dehydrogenase. 4. The association of L-asparagine and L-leucine exerted a sparing action on the utilization of endogenous amino acids, so that the integrated rate of nutrients oxidation was virtually identical in the sole presence of L-leucine and simultaneous presence of L-asparagine and L-leucine, respectively. 5. It is proposed that the enhancing action of L-asparagine upon insulin release evoked by L-leucine is attributable to an increased generation rate of cytosolic NADPH rather than any increase in nutrients oxidation. 相似文献