全文获取类型
收费全文 | 2631篇 |
免费 | 178篇 |
国内免费 | 95篇 |
出版年
2023年 | 16篇 |
2022年 | 40篇 |
2021年 | 33篇 |
2020年 | 37篇 |
2019年 | 47篇 |
2018年 | 63篇 |
2017年 | 56篇 |
2016年 | 53篇 |
2015年 | 62篇 |
2014年 | 141篇 |
2013年 | 301篇 |
2012年 | 101篇 |
2011年 | 116篇 |
2010年 | 109篇 |
2009年 | 155篇 |
2008年 | 143篇 |
2007年 | 160篇 |
2006年 | 114篇 |
2005年 | 123篇 |
2004年 | 107篇 |
2003年 | 85篇 |
2002年 | 85篇 |
2001年 | 69篇 |
2000年 | 50篇 |
1999年 | 46篇 |
1998年 | 51篇 |
1997年 | 45篇 |
1996年 | 45篇 |
1995年 | 38篇 |
1994年 | 30篇 |
1993年 | 34篇 |
1992年 | 24篇 |
1991年 | 18篇 |
1990年 | 25篇 |
1989年 | 19篇 |
1988年 | 18篇 |
1987年 | 19篇 |
1986年 | 11篇 |
1985年 | 34篇 |
1984年 | 31篇 |
1983年 | 31篇 |
1982年 | 34篇 |
1981年 | 19篇 |
1980年 | 16篇 |
1979年 | 17篇 |
1978年 | 9篇 |
1977年 | 6篇 |
1976年 | 8篇 |
1973年 | 3篇 |
1972年 | 3篇 |
排序方式: 共有2904条查询结果,搜索用时 31 毫秒
1.
Hyun I. Park 《Analytical biochemistry》2010,396(2):262-60
Matrix metalloproteinases (MMPs) are a family of hydrolytic enzymes that play significant roles in development, morphogenesis, inflammation, and cancer invasion. Endometase (matrilysin 2 or MMP-26) is a putative early biomarker for human carcinomas. The effects of the ionic and nonionic detergents on catalytic activity of endometase were investigated. The hydrolytic activity of endometase was detergent concentration dependent, exhibiting a bell-shaped curve with its maximum activity near the critical micelle concentration (CMC) of nonionic detergents tested. The effect of Brij-35 on human gelatinase B (MMP-9), matrilysin (MMP-7), and membrane-type 1 MMP (MT1-MMP) was further explored. Their maximum catalysis was observed near the CMC of Brij-35 (∼ 90 μM). Their IC50 values were above the CMC. The inhibition mechanism of MMP-7, MMP-9, and MT1-MMP by Brij-35 was a mixed type as determined by Dixon’s plot; however, the inhibition mechanism of endometase was noncompetitive with a Ki value of 240 μM. The catalytic activities of MMPs are influenced by detergents. Monomer of detergents may activate and stabilize MMPs to enhance catalysis, but micelle of detergents may sequester enzyme and block the substrate binding site to impede catalysis. Under physiological conditions, a lipid or membrane microenvironment may regulate enzymatic activity. 相似文献
2.
Filippo Genovese Stefania Ferrari Giambattista Guaitoli Monica Caselli M. Paola Costi Glauco Ponterini 《Protein science : a publication of the Protein Society》2010,19(5):1023-1030
An ad hoc bioconjugation/fluorescence resonance energy transfer (FRET) assay has been designed to spectroscopically monitor the quaternary state of human thymidylate synthase dimeric protein. The approach enables the chemoselective engineering of allosteric residues while preserving the native protein functions through reversible masking of residues within the catalytic site, and is therefore suitable for activity/oligomerization dual assay screenings. It is applied to tag the two subunits of human thymidylate synthase at cysteines 43 and 43′ with an excitation energy donor/acceptor pair. The dimer–monomer equilibrium of the enzyme is then characterized through steady‐state fluorescence determination of the intersubunit resonance energy transfer efficiency. 相似文献
3.
Reuben S.E. Young Andrew P. Bowman Kaylyn D. Tousignant Berwyck L.J. Poad Jennifer H. Gunter Lisa K. Philp Colleen C. Nelson Shane R. Ellis Ron M.A. Heeren Martin C. Sadowski Stephen J. Blanksby 《Journal of lipid research》2022,63(6):100223
The cellular energy and biomass demands of cancer drive a complex dynamic between uptake of extracellular FAs and their de novo synthesis. Given that oxidation of de novo synthesized FAs for energy would result in net-energy loss, there is an implication that FAs from these two sources must have distinct metabolic fates; however, hitherto, all FAs have been considered part of a common pool. To probe potential metabolic partitioning of cellular FAs, cancer cells were supplemented with stable isotope-labeled FAs. Structural analysis of the resulting glycerophospholipids revealed that labeled FAs from uptake were largely incorporated to canonical (sn-) positions on the glycerol backbone. Surprisingly, labeled FA uptake also disrupted canonical isomer patterns of the unlabeled lipidome and induced repartitioning of n-3 and n-6 PUFAs into glycerophospholipid classes. These structural changes support the existence of differences in the metabolic fates of FAs derived from uptake or de novo sources and demonstrate unique signaling and remodeling behaviors usually hidden from conventional lipidomics. 相似文献
4.
Ding-Kwo Chang Shu-Fang Cheng Chi-Hui Lin EricAssen B. Kantchev Cheng-Wei Wu 《生物化学与生物物理学报:生物膜》2005,1712(1):37-51
Two glutamic acid-rich fusion peptide analogs of influenza hemagglutinin were synthesized to study the organization of the charged peptides in the membranous media. Fluorescence and gel electrophoresis experiments suggested a loose association between the monomers in the vesicles. A model was built which showed that a positional difference of 3, 7 and 4, 8 results in the exposure of Glu3 and Glu7 side chains to the apolar lipidic core. Supportive results include: first, pKa values of two pH units higher than reference value in aqueous medium for Glu3 and Glu7 CγH, whereas the deviation of pKa from the reference value for Glu4 and Glu8 CγH is substantially smaller; second, Hill coefficients of titration shift of these protons indicate anti-cooperativity for Glu3 and Glu7 side chain protons but less so for Glu4 and Glu8, implying a strong electrostatic interaction between Glu3 and Glu7 possibly resulting from their localization in an apolar environment; third, positive and larger titration shift for NH of Glu3 is observed compared to that of Glu4, suggesting stronger hydrogen bond between the NH and the carboxylic group of Glu3 than that of Glu4, consistent with higher degree of exposure to hydrophobic medium for the side chain of Glu3. 相似文献
5.
M. Masuyama 《Biometrical journal. Biometrische Zeitschrift》1991,33(6):725-733
A mathematical model of the linearized growth curve and its physiological interpretation by the introduction of proper age, which is proportional to the chronological age, are presented here. In the second phase, but not in the first phase, this constant of proportionality is highly correlated with the age at menarche. 相似文献
6.
P. Usobiaga J. J. Calvete J. L. Saíz M. T. Eirín J. González-Rodríguez 《European biophysics journal : EBJ》1987,14(4):211-218
Sedimentation equilibrium and low-angle laser-light scattering were used to determine the molar mass of the glycoprotein moieties in the complexes of sodium dodecyl sulphate with the human platelet membrane glycoproteins IIb (GPIIb), IIIa (GPIIIa), and the (GPIIb) and (GPIIb) subunits of GPIIb. The values obtained by both procedures, except those for GPIIb, agree within experimental error with those calculated from their chemical composition: GPIIb (114,000 g mol-1), GPIIb (22,200 g mol-1), and GPIIIa (91,500 g mol-1). The molar mass of GPIIb determined by light scattering (142,000 g mol-1) and sedimentation equilibrium at different solvent densities (134,000 g mol-1) also agree, within experimental error, with the values calculated either from its chemical composition (136,500 g mol-1) or from the sum of the molar masses of its subunits. However the molar mass determined by sedimentation equilibrium at constant solvent density, is consistently underestimated (116,000 g mol-1).High-performance size-exclusion chromatography in sodium dodecyl sulphate solutions overestimates the molar mass of these glycoproteins and their Stokes radii, and therefore the maximal frictional ratios derived from them.Abbreviations GPIIb
glycoprotein IIb
- GPIIIa
glycoprotein IIIa
- GPIIb and GPIIb
and subunits of GPIIb, respectively
- CM-GPIIb
CM-GPIIb, and CM-GPIIIa, totally reduced and carboxymethylated forms of GPIIb, GPIIb, and GPIIIa, respectively
- SDS
sodium dodecyl sulphate
- eosin-ITC
eosin-5-isothiocyanate 相似文献
7.
D. L. Zhang K. Q. Li W. Gu L. F. Hao 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1987,75(1):132-137
Summary Different phytohormone concentrations induced different fequencies of various chromosome aberrations in calli of Vicia faba. NAA 10 ppm plus KT 2.5 ppm produced more haploids and NAA 30 ppm plus NAA 7.5 ppm produced more tetraploids and breakage. The relationship among the aberrations was analyzed. The hypothesis of ploidy equilibrium was established. The chromosome doubling rate and reduction rate of each treated group were calculated in relation to the observed data and the hypothesis. The frequency of tetraploids and breakage are correlated with each other. The frequency of total aberrations is linearly correlated with that of micronucleus formation. The regression equation is x=31.92+ 10.67 y. 相似文献
8.
Scavenging of superoxide radical by ascorbic acid 总被引:1,自引:0,他引:1
Using acetaldehyde and xanthine oxidase as the source of suPeroxide radical, the second order rate constant for the reaction
between ascorbic acid and superoxide radical was estimated to be 8.2 X 107 M-1 s-1. In rats, the average tissue concentration of ascorbic acid was of the order of 10-3 M and that of superoxide dismutase was of the order of 10-6 M. So, taking together both the rate constants and the tissue concentrations, the efficacy of ascorbic acid for scavenging
superoxide radical in animal tissues appears to be better than that of suPeroxide dismutase. The significance of ascorbic
acid as a scavenger of superoxide radical has been discussed from the point of view of the evolution of ascorbic acid synthesizing
capacity of terrestrial vertebrates. 相似文献
9.
白纹伊蚊幼虫龄期的发育历期 总被引:2,自引:0,他引:2
在实验室内20±1℃, 23±1℃, 25±1℃, 28±1℃和30±1℃恒温条件下, 观察了白纹伊蚊(Aedes albopictus)幼虫(广州株)的发育历期.幼虫的总发育历期和各龄幼虫的发育历期随温度的上升而缩短, 各龄幼虫历期在总发育历期中占有恒定的百分比, 据此计算出其捕获机率.各龄幼虫的发育历期与温度呈直线回归关系.通过积温公式, 求出各龄幼虫的积温常数.此外还探索了营养对幼虫发育历期的影响, 从而影响各龄幼虫捕获机率的计算. 相似文献
10.
Judit Kapocsi George T. Somogyi Nandor Ludvig Peter Serfozo Laszlo G. Harsing Jr. Russell J. Woods E. Sylvester Vizi 《Neurochemical research》1987,12(2):141-147
Neurochemical and pharmacological evidence has been obtained that noradrenergic varicosities (in mouse and rat vas deferens) and cholinergic varicosities (in the Auerbach's plexus) contain heterogenous alpha2-adrenoceptors through which the release of [3H]noradrenaline and [3H]acetylcholine can be modulated. The quantitative data also support the hypothesis that different noradrenaline and xylazine sensitive alpha2-adrenoceptors are present prejunctionally in the vas deferens and Auerbach's plexus preparations. Prazosin, although it has a presynaptic inhibitory effect on alpha2-adrenoceptors of noradrenergic axon terminals, has no effect on cholinergic axon terminals. These data suggest that there are two different types of alpha2-adrenoceptors at the presynaptic axon terminals.Special Issue Dedicated to Dr. Abel Lajtha 相似文献