全文获取类型
收费全文 | 490篇 |
免费 | 48篇 |
专业分类
538篇 |
出版年
2022年 | 6篇 |
2021年 | 4篇 |
2020年 | 7篇 |
2019年 | 5篇 |
2018年 | 5篇 |
2017年 | 8篇 |
2016年 | 11篇 |
2015年 | 15篇 |
2014年 | 15篇 |
2013年 | 24篇 |
2012年 | 30篇 |
2011年 | 22篇 |
2010年 | 18篇 |
2009年 | 10篇 |
2008年 | 30篇 |
2007年 | 27篇 |
2006年 | 16篇 |
2005年 | 19篇 |
2004年 | 17篇 |
2003年 | 31篇 |
2002年 | 23篇 |
2001年 | 23篇 |
2000年 | 19篇 |
1999年 | 21篇 |
1998年 | 6篇 |
1997年 | 7篇 |
1996年 | 8篇 |
1995年 | 6篇 |
1994年 | 4篇 |
1993年 | 4篇 |
1992年 | 15篇 |
1991年 | 6篇 |
1990年 | 11篇 |
1989年 | 9篇 |
1988年 | 5篇 |
1987年 | 5篇 |
1986年 | 3篇 |
1985年 | 11篇 |
1984年 | 6篇 |
1983年 | 4篇 |
1982年 | 3篇 |
1981年 | 3篇 |
1978年 | 1篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1973年 | 3篇 |
1972年 | 6篇 |
1963年 | 1篇 |
1933年 | 1篇 |
排序方式: 共有538条查询结果,搜索用时 15 毫秒
61.
Brison Y Pijning T Malbert Y Fabre É Mourey L Morel S Potocki-Véronèse G Monsan P Tranier S Remaud-Siméon M Dijkstra BW 《The Journal of biological chemistry》2012,287(11):7915-7924
ΔN123-glucan-binding domain-catalytic domain 2 (ΔN123-GBD-CD2) is a truncated form of the bifunctional glucansucrase DSR-E from Leuconostoc mesenteroides NRRL B-1299. It was constructed by rational truncation of GBD-CD2, which harbors the second catalytic domain of DSR-E. Like GBD-CD2, this variant displays α-(1→2) branching activity when incubated with sucrose as glucosyl donor and (oligo-)dextran as acceptor, transferring glucosyl residues to the acceptor via a ping-pong bi-bi mechanism. This allows the formation of prebiotic molecules containing controlled amounts of α-(1→2) linkages. The crystal structure of the apo α-(1→2) branching sucrase ΔN123-GBD-CD2 was solved at 1.90 Å resolution. The protein adopts the unusual U-shape fold organized in five distinct domains, also found in GTF180-ΔN and GTF-SI glucansucrases of glycoside hydrolase family 70. Residues forming subsite −1, involved in binding the glucosyl residue of sucrose and catalysis, are strictly conserved in both GTF180-ΔN and ΔN123-GBD-CD2. Subsite +1 analysis revealed three residues (Ala-2249, Gly-2250, and Phe-2214) that are specific to ΔN123-GBD-CD2. Mutation of these residues to the corresponding residues found in GTF180-ΔN showed that Ala-2249 and Gly-2250 are not directly involved in substrate binding and regiospecificity. In contrast, mutant F2214N had lost its ability to branch dextran, although it was still active on sucrose alone. Furthermore, three loops belonging to domains A and B at the upper part of the catalytic gorge are also specific to ΔN123-GBD-CD2. These distinguishing features are also proposed to be involved in the correct positioning of dextran acceptor molecules allowing the formation of α-(1→2) branches. 相似文献
62.
Wood K Paz A Dijkstra K Scheek RM Otten R Silman I Sussman JL Mulder FA 《Biomolecular NMR assignments》2012,6(1):15-18
Neuroligins act as heterophilic adhesion molecules at neuronal synapses. Their cytoplasmic domains interact with synaptic
scaffolding proteins, and have been shown to be intrinsically disordered. Here we report the backbone and side chain 1H, 13C and 15N resonance assignments for the cytoplasmic domain of human neuroligin 3. 相似文献
63.
Benjamin?D.?DuvalEmail author Joseph?C.?Blankinship Paul?Dijkstra Bruce?A.?Hungate 《Plant Ecology》2012,213(3):505-521
Elevated CO2 is expected to lower plant nutrient concentrations via carbohydrate dilution and increased nutrient use efficiency. Elevated
CO2 consistently lowers plant foliar nitrogen, but there is no consensus on CO2 effects across the range of plant nutrients. We used meta-analysis to quantify elevated CO2 effects on leaf, stem, root, and seed concentrations of B, Ca, Cu, Fe, K, Mg, Mn, P, S, and Zn among four plant functional
groups and two levels of N fertilization. CO2 effects on plant nutrient concentration depended on the nutrient, plant group, tissue, and N status. CO2 reduced B, Cu, Fe, and Mg, but increased Mn concentration in the leaves of N2 fixers. Elevated CO2 increased Cu, Fe, and Zn, but lowered Mn concentration in grass leaves. Tree leaf responses were strongly related to N status:
CO2 significantly decreased Cu, Fe, Mg, and S at high N, but only Fe at low N. Elevated CO2 decreased Mg and Zn in crop leaves grown with high N, and Mn at low N. Nutrient concentrations in crop roots were not affected
by CO2 enrichment, but CO2 decreased Ca, K, Mg and P in tree roots. Crop seeds had lower S under elevated CO2. We also tested the validity of a “dilution model.” CO2 reduced the concentration of plant nutrients 6.6% across nutrients and plant groups, but the reduction is less than expected
(18.4%) from carbohydrate accumulation alone. We found that elevated CO2 impacts plant nutrient status differently among the nutrient elements, plant functional groups, and among plant tissues.
Our synthesis suggests that differences between plant groups and plant organs, N status, and differences in nutrient chemistry
in soils preclude a universal hypothesis strictly related to carbohydrate dilution regarding plant nutrient response to elevated
CO2. 相似文献
64.
Although Europe is the cradle of dragonfly systematics and despite great progress in the last 2 decades, many issues in naming its species and understanding their evolutionary history remain unresolved. Given the public interest, conservation importance and scientific relevance of Odonata, it is time that remaining questions on the species?? status, names and affinities are settled. We review the extensive but fragmentary literature on the phylogeny, classification and taxonomy of European Odonata, providing summary phylogenies for well-studied groups and an ecological, biogeographic and evolutionary context where possible. Priorities for further taxonomic, phylogenetic and biogeographic research are listed and discussed. We predict that within a decade the phylogeny of all European species will be known. 相似文献
65.
V. S. Okken M. G. Niemeijer A. Dijkstra M. W. Baars S. Said K. Hoogenberg H. Orfgen S. Otten T. J. Cleophas 《Netherlands heart journal》2008,16(6):197-200
Background. In patients with hypertension noncompliance with drug treatment is between 15 to 54%, and has been recognised as a relevant contributor to the burden of cardiovascular morbidity. Up to 92% of patients experience unpleasant symptoms with their condition and, particularly in these patients, the symptoms experienced may enhance compliance. Objective. To simultaneously assess the effects of physical, social and psychological factors on noncompliance. Methods. Patients with mild hypertension despite drug treatment, from the departments of cardiology and internal medicine, were requested to answer a self-administered questionnaire addressing the presence of physical symptoms as well as psychosocial factors. The questionnaire was based on previously used test batteries and consisted of two lists of physical complaints and four lists addressing the four domains of planned behaviour regarding medical non-adherence according to Baron and Byrne. These domains mainly assess psychosocial factors. Each list consisted of three or more items and each item was scored on fiveto seven-point scales. Mean scores were used for assessment. The lists were also separately assessed for internal consistency and reliability using Cronbach’s alphas. One-way analysis of variance and multivariate analysis of variance (MANOVA) with compliance as outcome variable and the physical, social and psychological variables as indicator variables were used for data analysis. MANOVA was adjusted for multiple testing. Results. Many patients experienced physical symptoms due to hypertension, such as tiredness (31%), hot flushes (28%), headache (24%), reduced daily life energy (23%), palpitations (22%), with 95% confidence intervals between 16 to 38%. Scores for physical symptoms and social factors did not differ between self-reported adherers (n=165) and nonadherers (n=11). However, the score for psychological factors was significantly larger in the adherers than in the non-adherers, 5.05 versus 3.06, p<0.018. The MANOVA showed a significant overall difference between the adherers and non-adherers in the data at p<0.012, which was mainly due to the score for psychological factors. Conclusion. The effect of physical symptoms on non-compliance in mildly hypertensive patients is negligible. So is the effect of social factors. Psychological factors such as lacking a sense of guilt, regret and shame are major determinants of non-compliance. Physicians may play an educational role in improving their patients’ compliance by addressing these determinants. We should add that the conclusions should be made with reservations, given the small number of non-adherers in our sample. (Neth Heart J 2008;16:197-200.) 相似文献
66.
Yang L van der Werf KO Fitié CF Bennink ML Dijkstra PJ Feijen J 《Biophysical journal》2008,94(6):2204-2211
Micromechanical bending experiments using atomic force microscopy were performed to study the mechanical properties of native and carbodiimide-cross-linked single collagen fibrils. Fibrils obtained from a suspension of insoluble collagen type I isolated from bovine Achilles tendon were deposited on a glass substrate containing microchannels. Force-displacement curves recorded at multiple positions along the collagen fibril were used to assess the bending modulus. By fitting the slope of the force-displacement curves recorded at ambient conditions to a model describing the bending of a rod, bending moduli ranging from 1.0 GPa to 3.9 GPa were determined. From a model for anisotropic materials, the shear modulus of the fibril is calculated to be 33 ± 2 MPa at ambient conditions. When fibrils are immersed in phosphate-buffered saline, their bending and shear modulus decrease to 0.07-0.17 GPa and 2.9 ± 0.3 MPa, respectively. The two orders of magnitude lower shear modulus compared with the Young's modulus confirms the mechanical anisotropy of the collagen single fibrils. Cross-linking the collagen fibrils with a water-soluble carbodiimide did not significantly affect the bending modulus. The shear modulus of these fibrils, however, changed to 74 ± 7 MPa at ambient conditions and to 3.4 ± 0.2 MPa in phosphate-buffered saline. 相似文献
67.
Thorsten Eggert Christian Leggewie Michael Puls Wolfgang Streit Gertie van Pouderoyen Bauke W. Dijkstra Karl-erich Jaeger 《Biocatalysis and Biotransformation》2004,22(2):141-146
Enzymes produced from bacteria and eukaryotic organisms are presently being used for a large variety of different biotechnological applications. The rapidly increasing demand for enzymes which are active towards novel and often non-natural substrates has triggered the development of novel molecular biological methods of enzyme isolation and design. The metagenome approach is a cultivation-independent method which allows the direct cloning and expression of environmental DNA thereby providing access to a wealth of so-far unknown biocatalysts. Additionally, newly identified or existing biocatalysts can be further optimized by different methods of directed evolution. Here, the principle of the metagenome approach is outlined and a strategy is presented for the optimization of a bacterial lipase using a combination of rational design and directed evolution. 相似文献
68.
This study compared Pundamilia nyererei and Pundamilia pundamilia males in routine metabolic rate (RR) and in the metabolic costs males pay during territorial interactions (active metabolic rate, RA). Pundamilia nyererei and P. pundamilia males housed in social isolation did not differ in RR. In contrast to expectation, however, P. nyererei males used less oxygen than P. pundamilia males, for a given mass and level of agonistic activity. This increased metabolic efficiency may be an adaptation to limit the metabolic cost that P. nyererei males pay for their higher rate of aggressiveness compared to P. pundamilia males. Thus, the divergence between the species in agonistic behaviour is correlated with metabolic differentiation. Such concerted divergence in physiology and behaviour might be widespread in the dramatically diverse cichlid radiations in East African lakes and may be an important factor in the remarkably rapid speciation of these fishes. The results did not support the hypothesis that higher metabolic rates caused a physiological cost to P. nyererei males that would offset their dominance advantage. 相似文献
69.
Frits Roerdink Jan Dijkstra Ger Hartman Ben Bolscher Gerrit Scherphof 《Biochimica et Biophysica Acta (BBA)/General Subjects》1981,677(1):79-89
125I-labeled albumin or poly(vinyl pyrrolidone) encapsulated in intermediate size multilamellar or unilamellar liposomes with 30–40% of cholesterol were injected intravenously into rats. In other experiments liposomes containing phosphatidyl[Me-14C]choline were injected. 1 h after injection parenchymal or non-parenchymal cells were isolated. Non-parenchymal cells were separated by elutriation centrifugation into a Kupffer cell fraction and an endothelial cell fraction. From the measurements of radioactivities in the various cell fractions it was concluded that the liposomes are almost exclusively taken up by the Kupffer cells. Endothelial cells did not contribute at all and hepatocytes only to a very low extent to total hepatic uptake of the 125I-labels. Of the 14C-label, which orginates from the phosphatidylcholine moiety of the liposomes, much larger proportions were recovered in the hepatocytes. A time-dependence study suggested that besides the involvement of phosphatidylcholine exchange between liposomes and high density lipoprotein, a process of intercellular transfer of lipid label from Kupffer cells to the hepatocytes may be involved in this phenomenon. Lanthanum or gadolinium salts, which effectively block Kupffer cell activity, failed to accomplish an increase in the fraction of liposomal material recovered in the parenchymal cells. This is compatible with the notion that liposomes of the type used in these experiments have no, or at most very limited, access to the liver parenchyma following their intravenous administration to rats. 相似文献
70.
Marijke Haas Frits Moolenaar Alex C.A Kluppel Durk Dijkstra Dirk K.F Meijer Dick de Zeeuw 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1997,693(2):265
One possibility to optimize the therapeutic application of dopaminergic compounds with a catechol function is the reversible protection of this moiety using a prodrug approach. Important features in this respect are a proper chemical stability in the gastrointestinal tract, an adequate release rate after arrival in the blood stream or the possibility to cross the blood–brain barrier. A HPLC method was developed to measure the hydrolysis of prodrugs of dopamine and epinine directly. The method is based on reversed-phase separation followed by post-column ion-pair extraction with a fluorescent counter-ion. The separation of di-isobutyryl esters of dopamine and epinine is obtained within 10 min while the more hydrophobic dopaminergic esters, di-benzoyl and di-pivaloyl dopamine, are retained for 30 min. The precision of the assay measuring 160 ng dibudop and 100 ng ibopamine was 1.2 and 1.0%, respectively. The detection limit of all prodrugs tested was approximately 10 ng. 相似文献