全文获取类型
收费全文 | 2248篇 |
免费 | 270篇 |
国内免费 | 429篇 |
出版年
2024年 | 7篇 |
2023年 | 68篇 |
2022年 | 54篇 |
2021年 | 88篇 |
2020年 | 121篇 |
2019年 | 130篇 |
2018年 | 160篇 |
2017年 | 125篇 |
2016年 | 105篇 |
2015年 | 109篇 |
2014年 | 146篇 |
2013年 | 214篇 |
2012年 | 97篇 |
2011年 | 106篇 |
2010年 | 119篇 |
2009年 | 144篇 |
2008年 | 141篇 |
2007年 | 116篇 |
2006年 | 117篇 |
2005年 | 101篇 |
2004年 | 76篇 |
2003年 | 57篇 |
2002年 | 63篇 |
2001年 | 50篇 |
2000年 | 46篇 |
1999年 | 51篇 |
1998年 | 50篇 |
1997年 | 38篇 |
1996年 | 30篇 |
1995年 | 30篇 |
1994年 | 30篇 |
1993年 | 21篇 |
1992年 | 26篇 |
1991年 | 20篇 |
1990年 | 20篇 |
1989年 | 11篇 |
1988年 | 12篇 |
1987年 | 7篇 |
1986年 | 8篇 |
1985年 | 2篇 |
1984年 | 9篇 |
1983年 | 4篇 |
1982年 | 5篇 |
1981年 | 3篇 |
1980年 | 5篇 |
1979年 | 3篇 |
1976年 | 1篇 |
1973年 | 1篇 |
排序方式: 共有2947条查询结果,搜索用时 15 毫秒
101.
Li-Quan Yang Peng Sang Yan Tao Yun-Xin Fu Ke-Qin Zhang 《Journal of biomolecular structure & dynamics》2013,31(3):372-393
Proteins are dynamic entities in cellular solution with functions governed essentially by their dynamic personalities. We review several dynamics studies on serine protease proteinase K and HIV-1 gp120 envelope glycoprotein to demonstrate the importance of investigating the dynamic behaviors and molecular motions for a complete understanding of their structure–function relationships. Using computer simulations and essential dynamic (ED) analysis approaches, the dynamics data obtained revealed that: (i) proteinase K has highly flexible substrate-binding site, thus supporting the induced-fit or conformational selection mechanism of substrate binding; (ii) Ca2+ removal from proteinase K increases the global conformational flexibility, decreases the local flexibility of substrate-binding region, and does not influence the thermal motion of catalytic triad, thus explaining the experimentally determined decreased thermal stability, reduced substrate affinity, and almost unchanged catalytic activity upon Ca2+ removal; (iii) substrate binding affects the large concerted motions of proteinase K, and the resulting dynamic pocket can be connected to substrate binding, orientation, and product release; (iv) amino acid mutations 375 S/W and 423 I/P of HIV-1 gp120 have distinct effects on molecular motions of gp120, facilitating 375 S/W mutant to assume the CD4-bound conformation, while 423 I/P mutant to prefer for CD4-unliganded state. The mechanisms underlying protein dynamics and protein–ligand binding, including the concept of the free energy landscape (FEL) of the protein–solvent system, how the ruggedness and variability of FEL determine protein’s dynamics, and how the three ligand-binding models, the lock-and-key, induced-fit, and conformational selection are rationalized based on the FEL theory are discussed in depth. 相似文献
102.
本文研究了华北棉花-玉米农田景观格局中龟纹瓢虫Propylaea japonica(Thunberg)和异色瓢虫Harmonia axyridis(Pallas)种群动态,发现农田景观格局中作物类型(棉花与玉米)对两种瓢虫种群密度动态有显著的影响,两种天敌瓢虫都趋向在玉米斑块上栖息。两种瓢虫在棉花斑块上呈现出时间分化,其中龟纹瓢虫在棉花种植的前中期种群密度较大,后期较少;而异色瓢虫在棉花前中期种群密度较少,后期较多,表明农田景观中种植玉米有利于增强瓢虫对棉花害虫的控制作用。进一步的研究表明,农田景观系统中玉米斑块所占的面积比对龟纹瓢虫和异色瓢虫种群密度均产生显著影响。这说明在农田景观系统中开展区域性生态调控的时候,需要考虑到各类斑块组合的面积比例,从而有利于增强多种天敌昆虫的协调控害作用。 相似文献
103.
《Chronobiology international》2013,30(3):331-347
With the introduction of sustained-release theophyllíne formulations for once-daily dosing or for unequally divided twice-daily dosing, comparison with conventional equally divided twice-daily dosing has been focused on nocturnal serum theophylline concentrations (STCs), plateau properties and peak-trough fluctuation. The merits of various steady-state characteristics such as nocturnal excess, plateau time, residual concentration, peak-trough fluctuation, swing and AUC fluctuation are illustrated by 15 data sets from 7 multiple-dose studies, each including either 10–12 healthy volunteers or 12–20 COPD-patients. In all of the studies, STCs were determined at least every 2 hr over a 24-hr period in steady-state. Included in the studies were 7 sustained-release theophylline formulations which were administered either once daily (in the morning or in the evening), or twice daily (either equally divided, or unequally divided with one-third of the dose being given in the morning and two-thirds in the evening). 相似文献
104.
Under natural conditions, plants are subjected to continuous changes of irradiance that drive variations of stomatal conductance to water vapour (gs). We propose a dynamic model to predict the temporal response of gs at the leaf level using an asymmetric sigmoid function with a unique parameter describing time constants for increasing and decreasing gs. The model parameters were adjusted to observed data using Approximate Bayesian Computation. We tested the model performance for (1) instant changes of irradiance; or (2) continuous and controlled variations of irradiance simulating diurnal time courses. Compared with the two mostly used steady‐state models, our dynamic model described daily time courses of gs with a higher accuracy. In particular, it was able to describe the hysteresis of gs responses to increasing/decreasing irradiance and the resulting rapid variations of intrinsic water‐use efficiency. Compared to the mechanistic model of temporal responses of gs by Kirschbaum, Gross & Pearcy, for which time constants were estimated with a large variance, our model estimated time constants with a higher precision. It is expected to improve predictions of water loss and water‐use efficiency in higher scale models by using a small number of parameters. 相似文献
105.
Ana C. Santos Joana Cunha F. Veiga A. Cordeiro-da-Silva Antonio J. Ribeiro 《Carbohydrate polymers》2013
Alginate-dextran sulfate (ADS) microgel has been used to protect insulin from gastrointestinal attack and as a carrier to promote insulin permeation through intestinal epithelium. The throughput of ADS submicron particles generation by emulsification/internal gelation is limited by its wide size distribution. 相似文献
106.
The miniaturized wireless inertial measurement unit (IMU) technology and algorithms presented herein promote rapid and accurate predictions of the center-of-rotation (CoR) for ball/spherical joints. The algorithm improves upon existing IMU-based methods by directly utilizing the measured acceleration and angular velocity provided by the IMU to deduce the CoR in lieu of relying on error-prone velocity and position estimates. Results demonstrate that this new method resolves the position of the CoR to within a 3 mm sphere of the true CoR determined by a precision coordinate measuring machine. Such accuracy may render this method attractive for broad use in field, laboratory and clinical settings requiring non-invasive and rapid estimates of joint CoR. 相似文献
107.
108.
Nikki. L. Farnsworth Lorena R. Antunez Stephanie J. Bryant 《Biotechnology and bioengineering》2013,110(7):2046-2057
Dynamic loading has emerged as an important part of cartilage tissue engineering strategies for enhancing tissue production and producing cartilage with functionally competent mechanical properties. As patients in need of cartilage span a range of age groups, questions arise as to the role of age in a cell's ability to respond to dynamic loading. Therefore, this study's goal was to characterize age‐related anabolic and catabolic responses of chondrocytes to dynamic compressive loading. Bovine chondrocytes isolated from juvenile (3‐week‐old) and adult (2‐ to 3‐year‐old) donors were encapsulated in poly(ethylene glycol) hydrogels and subjected to dynamic loading applied intermittently in a sinusoidal waveform at 1 or 0.3 Hz with 5 or 10% amplitude strain up to 2 weeks. Loading significantly enhanced total sulfated glycosaminoglycan (sGAG) production by 220% for juvenile chondrocytes with 0.3 Hz/5% loading and by 88% for adult chondrocytes with 1 Hz/5% loading, while all other loading regimes did not affect or inhibited total sGAG production. Contrarily, deposition of larger matrix molecules of aggrecan and collagen II was either not affected or inhibited by loading. Collagen VI deposition was significantly upregulated by loading but only in adult chondrocytes and under different loading regimes (1 Hz/10% and 0.3 Hz/5%) when compared to total sGAGs. Both cell populations displayed catabolic activity, which appeared to be stimulated by loading. Taken together, findings from this study suggest that loading differentially regulates matrix synthesis and the response is highly dependent on donor age. Biotechnol. Bioeng. 2013; 110: 2046–2057. © 2013 Wiley Periodicals, Inc. 相似文献
109.
Ashley Slocum Mike Burnham Paul Genest Adith Venkiteshwaran Dayue Chen Joseph Hughes 《Biotechnology and bioengineering》2013,110(1):229-239
Virus‐removal filtration technology is commonly used in the manufacturing process for biologics to remove potential viral contaminants. Virus‐removal filters designed for retaining parvovirus, one of the smallest mammalian viruses, are considered an industry standard as they can effectively remove broad ranges of viruses. It has long been observed that the performance of virus filters can be influenced by virus preparations used in the laboratory scale studies (PDA, 2010 ). However, it remains unclear exactly what quality attributes of virus preparations are critical or indicative of virus filter performance as measured by effectiveness of virus removal and filter capacity consistency. In an attempt to better understand the relationship between virus preparation and virus filter performance, we have systematically prepared and analyzed different grades of parvovirus with different purity levels and compared their performance profiles on Viresolve® Pro parvovirus filters using four different molecules. Virus preparations used in the studies were characterized using various methods to measure DNA and protein content as well as the hydrodynamic diameter of virus particles. Our results indicate that the performance of Viresolve® Pro filters can be significantly impacted depending on the purity of the virus preparations used in the spike and recovery studies. More importantly, we have demonstrated that the purity of virus preparations is directly correlated to the measurable biochemical and biophysical properties of the virus preparations such as DNA and protein content and monodispersal status, thus making it possible to significantly improve the consistency and predictability of the virus filter performance during process step validations. Biotechnol. Bioeng. 2013; 110: 229–239. © 2012 Wiley Periodicals, Inc. 相似文献
110.
Clare E.M. Stevenson Richard K. Hughes Michael T. McManus David M. Lawson Stanislav Kopriva 《FEBS letters》2013
Sulfonucleotide reductases catalyse the first reductive step of sulfate assimilation. Their substrate specificities generally correlate with the requirement for a [Fe4S4] cluster, where adenosine 5′-phosphosulfate (APS) reductases possess a cluster and 3′-phosphoadenosine 5′-phosphosulfate reductases do not. The exception is the APR-B isoform of APS reductase from the moss Physcomitrella patens, which lacks a cluster. The crystal structure of APR-B, the first for a plant sulfonucleotide reductase, is consistent with a preference for APS. Structural conservation with bacterial APS reductase rules out a structural role for the cluster, but supports the contention that it enhances the activity of conventional APS reductases. 相似文献