首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   1939篇
  免费   101篇
  2023年   10篇
  2022年   6篇
  2021年   32篇
  2020年   21篇
  2019年   36篇
  2018年   55篇
  2017年   58篇
  2016年   67篇
  2015年   103篇
  2014年   98篇
  2013年   148篇
  2012年   161篇
  2011年   149篇
  2010年   100篇
  2009年   73篇
  2008年   132篇
  2007年   132篇
  2006年   110篇
  2005年   120篇
  2004年   110篇
  2003年   114篇
  2002年   75篇
  2001年   10篇
  2000年   7篇
  1999年   6篇
  1998年   19篇
  1997年   10篇
  1996年   9篇
  1995年   11篇
  1994年   10篇
  1993年   5篇
  1992年   6篇
  1991年   8篇
  1990年   7篇
  1989年   1篇
  1985年   5篇
  1984年   4篇
  1983年   2篇
  1982年   1篇
  1981年   4篇
  1980年   1篇
  1979年   1篇
  1978年   1篇
  1975年   1篇
  1973年   1篇
排序方式: 共有2040条查询结果,搜索用时 15 毫秒
61.
The aim of this study was to determine the effect of a polyphenol product (PP) (Proviox) and vitamin E on the antioxidant status and meat quality of broiler chickens exposed to high temperature. The experimental materials comprised 120 ROSS 308 broilers (6 treatments, 10 replications, 2 birds per replication). Dietary supplementation with vitamin E and PP was applied in the following experimental design: group I (negative control) – without supplementation; group II (positive control) – without supplementation; group III – supplementation with 100 mg vitamin E/kg; group IV – 200 mg vitamin E/kg; group V – 100 mg vitamin E/kg and 100 mg PP/kg; group VI – 200 mg PP/kg. In groups II–VI, broiler chickens aged 21–35 d were exposed to increased temperature (34°C for 10 h daily). In chickens exposed to high temperature, dietary supplementation with antioxidants, mostly PP, improved growth performance parameters, including body weight, body weight gain and feed intake until 28 d of age. Vitamin E added to broiler chicken diets at 200 mg/kg and vitamin E combined with PP was most effective in improving the total antioxidant status of birds, enhancing blood antioxidant enzyme activities and increasing vitamin E concentrations in the liver and breast muscles. Broilers fed diets supplemented with 200 mg/kg of vitamin E alone and vitamin E in combination with PP were characterised by a higher percentage content of breast muscles in the carcass. Dietary supplementation with antioxidants improved the water-holding capacity of meat, reduced natural drip loss and increased the crude ash content of meat. The breast muscles of chickens fed diets supplemented with PP had a lower contribution of yellowness. The breast muscles of chickens receiving diets with 100 mg vitamin E/kg(group III) and diets supplemented with PP (groups V and VI) were characterised by the highest concentrations of polyunsaturated fatty acids. The PP can be a valuable component of diets for broiler chickens exposed to high temperature.  相似文献   
62.
A cationic derivative of γ-cyclodextrin (GCD) modified with propylenediamine (PDA) was synthesized. It was shown that the derivative (GCD–PDA) is mucoadhesive and resistant to the digestion with?∝-amylase indicating that it may constitute an efficient oral delivery vehicle. GCD-PDA formed an inclusion complex with berberine (BBR), an alkaloid displaying a multitude of beneficial physiological effects. The complexed BBR penetrates a lipid membrane easier than the free one. Both uncomplexed BBR and that complexed with GCD-PDA was delivered to normal (NMuMG) and cancerous (4T1) murine mammary gland cells. In the normal cells both free and complexed BBR was homogeneously dispersed in the cytoplasm and was nontoxic up to 131?μM. In the cancerous cells uncomplexed BBR was also homogeneously dispersed but it was toxic to about 25% of cells at 131?μM, while the GCD-PDA/BBR complex was preferably localized in lysosomes and its toxicity doubled at this concentration compared to that of free BBR. Moreover, free BBR and GCD-PDA/BBR showed even more efficient inhibitory effect against murine melanoma (B16-F10) cells than against 4T1 cells.  相似文献   
63.
Application of the air‐puff swept source optical coherence tomography (SS‐OCT) instrument to determine the influence of viscoelasticity on the relation between overall the air‐puff force and corneal apex displacement of porcine corneas ex vivo is demonstrated. Simultaneous recording of time‐evolution of the tissue displacement and air pulse stimulus allows obtaining valuable information related in part to the mechanical properties of the cornea. A novel approach based on quantitative analysis of the corneal hysteresis of OCT data is presented. The corneal response to the air pulse is assessed for different well‐controlled intraocular pressure (IOP) levels and for the progression of cross‐linking‐induced stiffness of the cornea. Micrometer resolution, fast acquisition and noncontact character of the air‐puff SS‐OCT measurements have potential to improve the in vivo assessment of mechanical properties of the human corneas.   相似文献   
64.
The insect kinins are present in a wide variety of insects and function as potent diuretic peptides, though they are subject to rapid degradation by internal peptidases. Insect kinin analogs incorporating stereochemical variants of (2S,4S)-4-aminopyroglutamate (APy), a cis-peptide bond motif, demonstrate significant activity in a cricket diuretic assay. Insect kinin analogs containing (2R,4R)-APy, (2S,4R)-APy and (2S,4S)-APy are essentially equipotent on an insect diuretic assay, with EC(50) values of about 10(-7)M, whereas the (2R,4S)-APy analog is at least 10-fold more potent (EC(50) = 7 x 10(-9)M). Conformational studies in aqueous solution indicate that the (2R,4S)-APy analog is considerably more flexible than the other three variants, which may explain its greater potency. The work identifies the optimal stereochemistry for the APy scaffold with which to design biostable, peptidomimetic analogs with the potential to disrupt critical insect kinin-regulated processes in insects.  相似文献   
65.
The paper concerns the problem of fitting mathematical models of cell signaling pathways. Such models frequently take the form of sets of nonlinear ordinary differential equations. While the model is continuous in time, the performance index used in the fitting procedure involves measurements taken at discrete time moments. Adjoint sensitivity analysis is a tool which can be used for finding the gradient of a performance index in the space of parameters of the model. In the paper, a structural formulation of adjoint sensitivity analysis called the generalized backpropagation through time (GBPTT) is used. The method is especially suited for hybrid, continuous-discrete time systems. As an example, we use the mathematical model NF-kappaB of the regulatory module, which plays a major role in the innate immune response in animals.  相似文献   
66.
Gram-negative bacteria release LPS, which activates Toll-like-receptor-4 (TLR4) in the host, initiating an inflammatory response to infection. Infection increases risk for thrombosis. Platelets contribute to defense from infection and to thrombosis. Experiments were designed to determine whether LPS, through TLR4 signaling, affects platelet phenotype. Platelet responses in wild-type (WT) mice and mice that lack the TLR4 gene (dTLR4) were compared following a single nonlethal injection of LPS (0.2 mg/kg iv). Compared with WT mice, mice without TLR4 had fewer circulating platelets with lower RNA content and were less responsive to thrombin-activated expression of P-selectin but were equally sensitive to aggregation or ATP secretion. One week following the LPS injection, the time it takes for the circulating platelet pool to turnover, the number of circulating platelets, thrombin-induced expression of P-selectin, and collagen-activated aggregation were increased comparably in both groups of mice. Therefore, the change of the platelet pool to an activated phenotype 1 wk after a single exposure to LPS appears to arise from a process that is independent of TLR4. The persistence of the effect 1 wk after the injection suggests that the changes reflect an action of LPS on megakaryocytes and their platelet progeny rather than on circulating platelets, which would have been cleared.  相似文献   
67.
Heparin belongs to glycosaminoglycans (GAGs), a class of periodic linear anionic polysaccharides, which are functionally important components of the extracellular matrix owing to their interactions with various protein targets. Heparin is known to be involved in many cell signaling processes, while the experimental data available for heparin are significantly more abundant than for other GAGs. At the same time, the length and conformational flexibility of the heparin represent major challenges for its theoretical analysis. Coarse-grained (CG) approaches, which enable us to extend the size- and time-scale by orders of magnitude owing to reduction of system representation, appear, therefore, to be useful in simulating these systems. In this work, by using umbrella-sampling molecular dynamics simulations, we derived and parameterized the CG backbone-local potentials of heparin chains and the orientational potentials for the interactions of heparin with amino acid side chains to be further included in the physics-based Unified Coarse-Grained Model of biological macromolecules. With these potentials, simulations of extracellular matrix processes where both heparin and multiple proteins participate will be possible.  相似文献   
68.
Magnetoreception is the ability of organisms to perceive magnetic fields in the surrounding environment and changes in its properties such as field direction, intensity and gradient, where the effect on organisms can manifest as an array of reactions. As the magnetic sense is found in many taxa, both evolutionarily young and old, it can be assumed that magnetoreception came into existence as one of the first sensory systems. Many studies on the effect of magnetic fields on fishes have considered both fishes that migrate for long distances and those that are more or less sedentary. Research has focused on tracing the perception of the geomagnetic field by fishes and understanding magnetic fields that are smaller and larger than the ambient Earth's geomagnetic field. The question of the effect of magnetic fields of values higher than the Earth's is gaining importance with the increasing effect of anthropogenic magnetic and electromagnetic fields in aquatic ecosystems. This review draws together the results of studies on the effect and reception of natural and human-generated magnetic fields on fishes at various stages of ontogeny, chronologically arranged from gametes, through embryonic development, embryonic and larval motor function, directional reactions of embryos and larvae, orientation of fishes, to the mechanisms of magnetic field reception. The present state of knowledge indicates a common nature of effect on various ontogenetic stages of fishes. However, understanding of the mechanisms of magnetic sense in fishes and its relevance for ecological outcomes highlights that further progress requires more detailed research.  相似文献   
69.

Background

During standard gene cloning, the recombinant protein appearing in bacteria as the result of expression leakage very often inhibits cell proliferation leading to blocking of the cloning procedure. Although different approaches can reduce transgene basal expression, the recombinant proteins, which even in trace amounts inhibit bacterial growth, can completely prevent the cloning process.

Methods

Working to solve the problem of DNase II-like cDNA cloning, we developed a novel cloning approach. The method is based on separate cloning of the 5′ and 3′ fragments of target cDNA into a vector in such a way that the short Multiple Cloning Site insertion remaining between both fragments changes the reading frame and prevents translation of mRNA arising as a result of promoter leakage. Subsequently, to get the vector with full, uninterrupted Open Reading Frame, the Multiple Cloning Site insertion is removed by in vitro restriction/ligation reactions, utilizing the unique restriction site present in native cDNA.

Results

Using this designed method, we cloned a coding sequence of AcDNase II that is extremely toxic for bacteria cells. Then, we demonstrated the usefulness of the construct prepared in this way for overexpression of AcDNase II in eukaryotic cells.

Conclusions

The designed method allows cloning of toxic protein coding sequences that cannot be cloned by standard methods.

General significance

Cloning of cDNAs encoding toxic proteins is still a troublesome problem that hinders the progress of numerous studies. The method described here is a convenient solution to cloning problems that are common in research on toxic proteins.  相似文献   
70.
With the advance of experimental procedures obtaining chemical crosslinking information is becoming a fast and routine practice. Information on crosslinks can greatly enhance the accuracy of protein structure modeling. Here, we review the current state of the art in modeling protein structures with the assistance of experimentally determined chemical crosslinks within the framework of the 13th meeting of Critical Assessment of Structure Prediction approaches. This largest-to-date blind assessment reveals benefits of using data assistance in difficult to model protein structure prediction cases. However, in a broader context, it also suggests that with the unprecedented advance in accuracy to predict contacts in recent years, experimental crosslinks will be useful only if their specificity and accuracy further improved and they are better integrated into computational workflows.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号