全文获取类型
收费全文 | 2275篇 |
免费 | 28篇 |
国内免费 | 33篇 |
专业分类
2336篇 |
出版年
2023年 | 23篇 |
2022年 | 14篇 |
2021年 | 21篇 |
2020年 | 41篇 |
2019年 | 17篇 |
2018年 | 39篇 |
2017年 | 18篇 |
2016年 | 18篇 |
2015年 | 64篇 |
2014年 | 82篇 |
2013年 | 132篇 |
2012年 | 61篇 |
2011年 | 132篇 |
2010年 | 103篇 |
2009年 | 152篇 |
2008年 | 142篇 |
2007年 | 154篇 |
2006年 | 104篇 |
2005年 | 98篇 |
2004年 | 83篇 |
2003年 | 63篇 |
2002年 | 53篇 |
2001年 | 28篇 |
2000年 | 37篇 |
1999年 | 42篇 |
1998年 | 45篇 |
1997年 | 43篇 |
1996年 | 43篇 |
1995年 | 47篇 |
1994年 | 40篇 |
1993年 | 33篇 |
1992年 | 32篇 |
1991年 | 44篇 |
1990年 | 36篇 |
1989年 | 23篇 |
1988年 | 24篇 |
1987年 | 20篇 |
1986年 | 11篇 |
1985年 | 19篇 |
1984年 | 29篇 |
1983年 | 18篇 |
1982年 | 34篇 |
1981年 | 19篇 |
1980年 | 21篇 |
1979年 | 22篇 |
1978年 | 3篇 |
1977年 | 5篇 |
1976年 | 1篇 |
1974年 | 2篇 |
1971年 | 1篇 |
排序方式: 共有2336条查询结果,搜索用时 15 毫秒
51.
Iron overload is a major health problem for patients who have to have continuous blood transfusions. It brings some metabolic problems together. Various iron chelating agents are being used for treatment of hemochromatosis which arises from excess iron accumulation. This study was conducted with the aim of determining whether deferasirox used as an iron chelator in patients with hemochromatosis has genotoxic effects. Commercial form of deferasirox, Exjade was used as test material. Test material showed a general mutagen character in mutant strains of Salmonella typhimurium. Deferasirox has also led to an increase in mutagenity-related polymorphic band count in random amplification of polymorphic DNA test done with bone marrow cells of rats. Similarly, test material has increased micronucleus formation in cultured in vitro human peripheral lymphocytes particularly in 48 h period. Consistently with the abovementioned findings, deferasirox reduced nuclear division index (NDI) compared to controls and some part of these reductions are statistically significant. NDI reductions were found at positive control levels at high concentrations. 相似文献
52.
Paul V. Bernhardt Piao Chin Philip C. Sharpe Jing-Yan C. Wang Des R. Richardson 《Journal of biological inorganic chemistry》2005,10(7):761-777
The search for orally effective drugs for the treatment of iron overload disorders is an important goal in improving the health
of patients suffering diseases such as β-thalassemia major. Herein, we report the syntheses and characterization of some new
members of a series of N-aroyl-N′-picolinoyl hydrazine chelators (the H2IPH analogs). Both 1:1 and 1:2 FeIII:L complexes were isolated and the crystal structures of Fe(HPPH)Cl2, Fe(4BBPH)Cl2, Fe(HAPH)(APH) and Fe(H3BBPH)(3BBPH) were determined (H2PPH=N,N′-bis-picolinoyl hydrazine; H2APH=N-4-aminobenzoyl-N′-picolinoyl hydrazine, H23BBPH=N-3-bromobenzoyl-N′-picolinoylhydrazine and H24BBPH=N-(4-bromobenzoyl)-N′-(picolinoyl)hydrazine). In each case, a tridentate N,N,O coordination mode of each chelator with Fe was observed. The FeIII complexes of these ligands have been synthesized and their structural, spectroscopic and electrochemical characterization
are reported. Five of these new chelators, namely H2BPH (N-(benzoyl)-N′-(picolinoyl)hydrazine), H2TPH (N-(2-thienyl)-N′-(picolinoyl)-hydrazine), H2PPH, H23BBPH and H24BBPH, showed high efficacy at mobilizing 59Fe from cells and inhibiting 59Fe uptake from the serum Fe transport protein, transferrin (Tf). Indeed, their activity was much greater than that found for
the chelator in current clinical use, desferrioxamine (DFO), and similar to that observed for the orally active chelator,
pyridoxal isonicotinoyl hydrazone (H2PIH). The ability of the chelators to inhibit 59Fe uptake could not be accounted for by direct chelation of 59Fe from 59Fe–Tf. The most effective chelators also showed low antiproliferative activity which was similar to or less than that observed
with DFO, which is important in terms of their potential use as agents to treat Fe-overload disease. 相似文献
53.
Björn Schwanhäusser Manfred Gossen Gunnar Dittmar Matthias Selbach Dr. 《Proteomics》2009,9(1):205-209
Current methods for system‐wide gene expression analysis detect changes in mRNA abundance, but neglect regulation at the level of translation. Pulse labeling with stable isotopes has been used to measure protein turnover rates, but this does not directly provide information about translation rates. Here, we developed pulsed stable isotope labeling by amino acids in cell culture (pSILAC) with two heavy isotope labels to directly quantify protein translation on a proteome‐wide scale. We applied the method to cellular iron homeostasis as a model system and demonstrate that it can confidently identify proteins that are translationally regulated by iron availability. 相似文献
54.
H. Drechsel M. Tschierske A. Thieken G. Jung H. Zähner G. Winkelmann 《Journal of industrial microbiology & biotechnology》1995,14(2):105-112
Summary Rhizoferrin is a novel carboxylate-type siderophore which has recently been isolated fromRhizopus microsporus and other fungi of the Mucorales (Zygomycetes). The present investigation shows that a variety of rhizoferrin analogs can be produced by directed fermentation. Thus both the diaminobutane backbone and the citric acid side chains of rhizoferrin have been substituted by diamine and citric acid analogs added to the culture medium. The new ligands as well as their iron complexes have been characterized by physicochemical methods. Conditions of precursor incorporation and implications for the biosynthesis of the new siderophores are discussed. 相似文献
55.
Roman Bo?a Peter Baran L'ubor Dlháň Hartmut Fuess Wolfgang Haase Franz Renz Wolfgang Linert Ingrid Svoboda Rüdiger Werner 《Inorganica chimica acta》1997,260(2):4119-136
The structure of the [Fe(bzimpy)2](ClO4)2·xH2O system (x = 0.25) was determined by single crystal X-ray structure analysis. The Fe(II) ion is hexacoordinated by six donor nitrogen atoms. The magnetic properties of the complex were investigated by powder magnetic susceptibility measurements and ESR. The freshly prepared sample does not show any traces of iron(III) impurities but these are formed as a function of time. After 1 year the sample contains 8.2% iron(III) as shown by UV spectroscopy and indicated by geff = 4.3 and 2.0 in its ESR spectrum. This explains the recorded ξ versus T behaviour at low temperature: with increasing temperature the ξ value decreases according to the Curie-Weiss law for a S = 5/2 system having an effective g = 4.3. Above 220 K a continuous increase in the ξ value is observed and a spin crossover applies. The spin transition is not complete at room temperature. A pronounced hysteresis is observed upon heating/cooling the sample between 220 and 414 K on the basis of magnetic data and infrared spectra. 相似文献
56.
Susana Estevez M Abele D Puntarulo S 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2002,132(4):243-737
Lipid peroxidation in Laternula elliptica was assessed by detecting lipid radicals by electronic paramagnetic resonance. The values were compared with data from the temperate mud clam Mya arenaria. Lipid radical content was higher in the Antarctic bivalve than in the temperate mud clam, even within the range of its habitat temperature. The rate of generation of lipid radicals was affected by the iron content in the samples. The iron content in individual samples of digestive glands in L. elliptica ranged from 3 to 6 nmol g−1 fresh weight (fwt) and in M. arenaria from 0.6 to 2.7 nmol g−1 fwt. Arrhenius plots, developed from the rates obtained in the presence of 25 μM iron, showed no significant differences between the activation energy calculated for digestive glands of L. elliptica and M. arenaria. The Fe3+ reduction rate in L. elliptica was higher than in M. arenaria (4.7±0.9 vs. 1.8±0.4 nmol mg−1 protein min−1, respectively). L. elliptica had a higher content of α-tocopherol and β-carotene than M. arenaria. Our data suggest that increased lipid radical content in the membranes of cold-adapted organisms could be related to iron content. 相似文献
57.
Summary Boron, copper, iron, manganese and zinc concentrations were measured in sunflower leaves from plants grown hydroponically
in a closed continuous flow system and with boron concentrations ranging from deficient to toxic.
Leaves were analyzed at the stage of flower development. There was a highly significant inverse correlation between B concentration
in solution and Mn concentration in leaves.
Cu, Fe and Zn concentrations in the leaves were not changed by the different B levels, although the B concentration in leaves
increased with an increasing concentration in solution, showing a close correlation each other. 相似文献
58.
Summary Dicotyledonous plants respond to Fe deficiency by enhancing the capacity of their roots to reduce Fe(III) to Fe(II). It has been suggested that there are two different ferric redox systems in the roots: the standard reductase, active with ferricyanide and not inducible by Fe deficiency, and the turbo reductase, active with both ferricyanide and ferric chelates and inducible by Fe deficiency. We have used different experimental approaches to test whether or not the Fe(III)-reducing capacity of cucumber (Cucumis sativus L. cv. Ashley) roots can be explained by considering the standard and the turbo reductase as the same enzyme. For this, we used both Fe-sufficient and Fe-deficient plants, which were treated with ethylene inhibitors (cobalt or silver thiosulfate; found to inhibit the turbo reductase in a previous work), a protein synthesis inhibitor (cycloheximide), or an mRNA polyadenylation inhibitor (cordycepin). At different times after application of these inhibitors, reduction of both ferricyanide and Fe(III)-EDTA were determined. In addition, we studied the effects of pH and temperature on the reduction of ferricyanide and Fe(III)-EDTA by both Fe-sufficient and Fe-deficient plants. Results suggest that there are, at least, two different ferric redox systems in the roots. Enhancement of Fe(III)-reducing capacity (turbo reductase) by Fe-deficient plants probably requires the de novo synthesis of a (or several) protein(s), which has a high turnover rate and whose expression is presumably regulated by ethylene.Abbreviations Ch-R
ferric chelate reductase
- CHM
cycloheximide
- CN-R
ferricyanide reductase
- EDDHA
N,N-ethylene bis[2-(2-hydroxyphenyl)-glycine]
- EDTA
ethylenediamine-tetraacetic acid
- Ferrozine
3-(2-pyridyl)-5,6-bis(4-phenylsulfonic acid)-1,2,4-triazine
- HEDTA
N-hydroxyethylethylene-diaminetriacetic acid
- STS
silver thiosulfate 相似文献
59.
Rapid and direct screening of nitrile-converting enzymes is of great importance in the development of industrial biocatalytic process for pharmaceuticals and fine chemicals. In this paper, a combination of ferrous and ferric ions was used to establish a novel colorimetric screening method for nitrile hydratase and amidase with α-amino nitriles and α-amino amides as substrates, respectively. Ferrous and ferric ions reacted sequentially with the cyanide dissociated spontaneously from α-amino nitrile solution, forming a characteristic deep blue precipitate. They were also sensitive to weak basicity due to the presence of amino amide, resulting in a yellow precipitate. When amino amide was further hydrolyzed to amino acid, it gave a light yellow solution. Mechanisms of color changes were further proposed. Using this method, two isolates with nitrile hydratase activity towards 2-amino-2,3-dimethyl butyronitrile, one strain capable of hydrating 2-amino-4-(hydroxymethyl phosphiny) butyronitrile and another microbe exhibiting amidase activity against 2-amino-4-methylsulfanyl butyrlamide were obtained from soil samples and culture collections of our laboratory. Versatility of this method enabled it the first direct and inexpensive high-throughput screening system for both nitrile hydratase and amidase. 相似文献
60.
Iron and citrate are essential for the metabolism of most organisms, and regulation of iron and citrate biology at both the
cellular and systemic levels is critical for normal physiology and survival. Mitochondrial and cytosolic aconitases catalyze
the interconversion of citrate and isocitrate, and aconitase activities are affected by iron levels, oxidative stress and
by the status of the Fe–S cluster biogenesis apparatus. Assembly and disassembly of Fe–S clusters is a key process not only
in regulating the enzymatic activity of mitochondrial aconitase in the citric acid cycle, but also in controlling the iron
sensing and RNA binding activities of cytosolic aconitase (also known as iron regulatory protein IRP1). This review discusses
the central role of aconitases in intermediary metabolism and explores how iron homeostasis and Fe–S cluster biogenesis regulate
the Fe–S cluster switch and modulate intracellular citrate flux. 相似文献