全文获取类型
收费全文 | 1073篇 |
免费 | 42篇 |
出版年
2023年 | 13篇 |
2022年 | 19篇 |
2021年 | 33篇 |
2020年 | 26篇 |
2019年 | 18篇 |
2018年 | 23篇 |
2017年 | 20篇 |
2016年 | 41篇 |
2015年 | 71篇 |
2014年 | 52篇 |
2013年 | 113篇 |
2012年 | 92篇 |
2011年 | 115篇 |
2010年 | 80篇 |
2009年 | 43篇 |
2008年 | 44篇 |
2007年 | 50篇 |
2006年 | 36篇 |
2005年 | 41篇 |
2004年 | 32篇 |
2003年 | 37篇 |
2002年 | 26篇 |
2001年 | 9篇 |
2000年 | 6篇 |
1999年 | 3篇 |
1998年 | 8篇 |
1997年 | 2篇 |
1996年 | 5篇 |
1995年 | 7篇 |
1994年 | 4篇 |
1993年 | 2篇 |
1992年 | 5篇 |
1991年 | 6篇 |
1990年 | 2篇 |
1988年 | 2篇 |
1987年 | 3篇 |
1986年 | 2篇 |
1985年 | 2篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1973年 | 1篇 |
1972年 | 3篇 |
1968年 | 4篇 |
1965年 | 1篇 |
1964年 | 1篇 |
排序方式: 共有1115条查询结果,搜索用时 15 毫秒
101.
Tapas?K?BasakEmail author Suman?Halder Madona?Kumar Renu?Sharma Bijoylaxmi?Midya 《Theoretical biology & medical modelling》2005,2(1):11
Background
The present paper describes a topological model of biofeedback. This model incorporates input from a sensory organ and a transduction phase mediated through catecholamine production in the feedback path. The transduction phase comprises both conservative and dissipative systems, from which the appropriate output is combined in a closed loop. 相似文献102.
This protocol describes an in vitro approach for measuring the kinetics and affinities of interactions between membrane-anchored proteins. This method is particularly established for dissecting the interaction dynamics of cytokines with their receptor subunits. For this purpose, the receptor subunits are tethered in an orientated manner onto solid-supported lipid bilayers by using multivalent chelator lipids. Interaction between the ligand with the receptor subunits was probed by a combination of surface-sensitive spectroscopic detection techniques. Label-free detection by reflectance interferometry is used for following assembly of the membrane and tethering of the receptor subunits in quantitative terms. Total internal reflection spectroscopy is used for monitoring ligand binding to the membrane-anchored receptor, for monitoring ligand-receptor interactions by FRET and for monitoring ligand-exchange kinetics. These assays can be used for determining the affinities and stabilities of ligand-receptor complexes in plane of the membrane. The techniques described in this protocol can be established in 2-3 months. 相似文献
103.
This protocol describes the synthesis of a lipid-like molecule carrying a head group containing two nitrilotriacetic acid moieties. This multivalent chelator lipid can be incorporated into lipid membranes, to which histidine-tagged protein can then be tethered in an oriented fashion. Possible applications of this lipid are protein tethering to solid-supported membranes, to lipid vesicles or to live cells. As compared to conventional monovalent chelator lipids, this lipid can achieve highly stable tethering of proteins by the multivalent chelator head. The eight-step synthesis described in this protocol can be completed within 4-5 weeks. 相似文献
104.
Disease state differentiation and identification of tuberculosis biomarkers via native antigen array profiling 总被引:3,自引:0,他引:3
Sartain MJ Slayden RA Singh KK Laal S Belisle JT 《Molecular & cellular proteomics : MCP》2006,5(11):2102-2113
A critical element of tuberculosis control is early and sensitive diagnosis of infection and disease. Our laboratories recently showed that different stages of disease were distinguishable via two-dimensional Western blot analyses of Mycobacterium tuberculosis culture filtrate proteins. However, this methodology is not suitable for high throughput testing. Advances in protein microarray technology provide a realistic mechanism to screen a large number of serum samples against thousands of proteins to identify biomarkers of disease states. Techniques were established for separation of native M. tuberculosis cytosol and culture filtrate proteins, resulting in 960 unique protein fractions that were used to generate protein microarrays. Evaluation of serological reactivity from 42 patients in three tuberculosis disease states and healthy purified protein derivative-positive individuals demonstrated that human immunodeficiency virus (HIV)-negative cavitary and noncavitary tuberculosis (TB) patients' sera recognized 126 and 59 fractions, respectively. Sera from HIV patients coinfected with TB recognized 20 fractions of which five overlapped with those recognized by non-HIV TB patients' sera and 15 were unique to the HIV+TB+ disease state. Identification of antigens within the reactive fractions yielded 11 products recognized by both cavitary and noncavitary TB patients' sera and four proteins (HspX, MPT64, PstS1, and TrxC) specific to cavitary TB patients. Moreover four novel B cell antigens (BfrB, LppZ, SodC, and TrxC) of human tuberculosis were identified. 相似文献
105.
We used PCRs with omp A primers to determine if spotted fever group rickettsiae occurred in Amblyomma variegatum from 6 Caribbean islands. Positive amplicons were obtained from ticks from the U.S. Virgin Islands (9/18; 50%), Dominica (39/171; 30%), Montserrat (2/5; 40%), Nevis (17/34; 50%), St. Kitts (46/227; 20%), and St. Lucia (1/14; 7%). Sequences for a convenience sample of reaction products obtained from A. variegatum on St. Kitts (7), American Virgin Islands (4), Montserrat (2), and St. Lucia (1) were 100% homologous with that of Rickettsia africae , the agent of African tick-bite fever. To determine if transmission of R. africae occurred, we used Rickettsia rickettsii antigen in IFA tests and found positive titers (≥ 1/80) with sera from cattle, goats, and sheep from Dominica (24/95 [25%], 2/136 [2%], 0/58 [0%]), Nevis (12/45 [27%], 5/157 [3%], 0/90 [0%]), St. Kitts (2/43 [5%], 1/25 [4%), 1/35 [3%]), and St. Lucia (6/184 [3%] cattle), respectively. No seropositive animals were found in Grenada (0/4, 0/98/, 0/86), Montserrat (0/12, 0/26, 0/52), or Puerto Rico (0/80 cattle). Our study indicates that R. africae and African tick-bite fever are widespread in the Caribbean. 相似文献
106.
Rakhee S. Gupte Dhawjbahadur K. Rawat Sukrutha Chettimada Donna L. Cioffi Michael S. Wolin William T. Gerthoffer Ivan F. McMurtry Sachin A. Gupte 《The Journal of biological chemistry》2010,285(25):19561-19571
Hypoxic pulmonary vasoconstriction (HPV) is a physiological response to a decrease in airway O2 tension, but the underlying mechanism is incompletely understood. We studied the contribution of glucose-6-phosphate dehydrogenase (Glc-6-PD), an important regulator of NADPH redox and production of reactive oxygen species, to the development of HPV. We found that hypoxia (95% N2, 5% CO2) increased contraction of bovine pulmonary artery (PA) precontracted with KCl or serotonin. Depletion of extracellular glucose reduced NADPH, NADH, and HPV, substantiating the idea that glucose metabolism and Glc-6-PD play roles in the response of PA to hypoxia. Our data also show that inhibition of glycolysis and mitochondrial respiration (indicated by an increase in NAD+ and decrease in the ATP-to-ADP ratio) by hypoxia, or by inhibitors of pyruvate dehydrogenase or electron transport chain complexes I or III, increased generation of reactive oxygen species, which in turn activated Glc-6-PD. Inhibition of Glc-6-PD decreased Ca2+ sensitivity to the myofilaments and diminished Ca2+-independent and -dependent myosin light chain phosphorylation otherwise increased by hypoxia. Silencing Glc-6-PD expression in PA using a targeted small interfering RNA abolished HPV and decreased extracellular Ca2+-dependent PA contraction increased by hypoxia. Similarly, Glc-6-PD expression and activity were significantly reduced in lungs from Glc-6-PDmut(−/−) mice, and there was a corresponding reduction in HPV. Finally, regression analysis relating Glc-6-PD activity and the NADPH-to-NADP+ ratio to the HPV response clearly indicated a positive linear relationship between Glc-6-PD activity and HPV. Based on these findings, we propose that Glc-6-PD and NADPH redox are crucially involved in the mechanism of HPV and, in turn, may play a key role in increasing pulmonary arterial pressure, which is involved in the development of pulmonary hypertension. 相似文献
107.
Khanna N Arora D Halder S Mehta AK Garg GR Sharma SB Mahajan P 《Indian journal of experimental biology》2010,48(3):299-305
Treatment with C. mukul and O. sanctum, showed a significant decrease in cholesterol and triglyceride levels respectively. O. sanctum also significantly increased serum HDL-cholesterol compared to control. Serum MDA levels were significantly reduced in all the treated groups compared to control suggesting that each of the drugs under study were effective in their free radical scavenging action. Erythrocyte SOD activity was increased in all the treatment groups with C. mukul showing the maximum effect followed by O. sanctum, folic acid and ramipril. The erythrocyte CAT activity was significantly increased in all the drug treated groups with maximum increase seen in O. sanctum and ramipril treated groups, whereas lesser effects were observed with C. mukul and folic acid groups. Thus, the indigenous drugs, C. mukul and O. sanctum had beneficial effect on hypercholesterolemic rabbit model, both in terms of lipid profile as well as antioxidant potential. Ocimum sanctum was found to be the most promising of all the drugs. Moreover, it could be hypothesized that these plant products along with folic acid and ramipril can be explored for synergistic effect for treatment for hypercholesterolemic conditions. 相似文献
108.
Suman Karki 《Carbohydrate research》2010,345(13):1958-3917
Kitasatospora kifunensis, the talosin producer, was used as a source for the dTDP-6-deoxy-l-talose (dTDP-6dTal) biosynthetic gene cluster, serving as a template for four recombinant proteins of RmlAKkf, RmlBKkf, RmlCKkf, and Tal, which complete the biosynthesis of dTDP-6dTal from dTTP, α-d-glucose-1-phosphate, and NAD(P)H. The identity of dTDP-6dTal was validated using 1H and 13C NMR spectroscopy. K. kifunensistal and tll, the known dTDP-6dTal synthase gene of Actinobacillus actinomycetemcomitans origin, have low sequence similarity and are distantly related within the NDP-6-deoxy-4-ketohexose reductase family, providing an example of the genetic diversity within the dTDP-6dTal biosynthetic pathway. 相似文献
109.
110.
Leguminous plants in the tropical rainforests are a rich source of proteinase inhibitors and this work illustrates isolation of a serine proteinase inhibitor from the seeds of Archidendron ellipticum (AeTI), inhabiting Great Nicobar Island, India. AeTI was purified to homogeneity by acetone and ammonium sulfate fractionation, and ion exchange, size exclusion and reverse phase chromatography (HPLC). SDS-PAGE of AeTI revealed that it is constituted by two polypeptide chains (alpha-chain, M(r) 15,000 and beta-chain, M(r) 5000), the molecular weight being approximately 20 kDa. N-terminal sequence showed high homology with other serine proteinase inhibitors belonging to the Mimosoideae subfamily. Both Native-PAGE as well as isoelectric focussing showed four isoinhibitors (pI values of 4.1, 4.55, 5.27 and 5.65). Inhibitory activity of AeTI remained unchanged over a wide range of temperatures (0-60 degrees C) and pH (1-10). The protein inhibited trypsin in the stoichiometric ratio of 1:1, but lacked similar stoichiometry against chymotrypsin. Also, AeTI-trypsin complex was stable to SDS unlike the SDS unstable AeTI-chymotrypsin complex. AeTI, which possessed inhibition constants (K(i)) of 2.46 x 10(-10) and 0.5 x 10(-10)M against trypsin and chymotrypsin activity, respectively, retained over 70% of inhibitory activity after being stored at -20 degrees C for more than a year. Initial studies on the insecticidal properties of AeTI indicate it to be a very potent insect anti-feedant. 相似文献