全文获取类型
收费全文 | 598篇 |
免费 | 38篇 |
国内免费 | 1篇 |
专业分类
637篇 |
出版年
2024年 | 4篇 |
2023年 | 4篇 |
2022年 | 6篇 |
2021年 | 9篇 |
2020年 | 4篇 |
2019年 | 5篇 |
2018年 | 12篇 |
2017年 | 12篇 |
2016年 | 15篇 |
2015年 | 14篇 |
2014年 | 34篇 |
2013年 | 39篇 |
2012年 | 40篇 |
2011年 | 38篇 |
2010年 | 28篇 |
2009年 | 18篇 |
2008年 | 27篇 |
2007年 | 27篇 |
2006年 | 19篇 |
2005年 | 23篇 |
2004年 | 15篇 |
2003年 | 18篇 |
2002年 | 18篇 |
2001年 | 18篇 |
2000年 | 14篇 |
1999年 | 7篇 |
1994年 | 4篇 |
1993年 | 5篇 |
1992年 | 11篇 |
1991年 | 11篇 |
1990年 | 8篇 |
1988年 | 6篇 |
1987年 | 5篇 |
1986年 | 5篇 |
1985年 | 13篇 |
1984年 | 7篇 |
1983年 | 6篇 |
1981年 | 9篇 |
1980年 | 8篇 |
1978年 | 6篇 |
1976年 | 3篇 |
1975年 | 3篇 |
1974年 | 4篇 |
1973年 | 5篇 |
1972年 | 6篇 |
1971年 | 6篇 |
1969年 | 4篇 |
1968年 | 3篇 |
1967年 | 4篇 |
1966年 | 4篇 |
排序方式: 共有637条查询结果,搜索用时 0 毫秒
81.
Delineating the Specific Influence of Virus Isoelectric Point and Size on Virus Adsorption and Transport through Sandy Soils 总被引:10,自引:4,他引:10 下载免费PDF全文
Scot E. Dowd Suresh D. Pillai Sookyun Wang M. Yavuz Corapcioglu 《Applied microbiology》1998,64(2):405-410
Many of the factors controlling viral transport and survival within the subsurface are still poorly understood. In order to identify the precise influence of viral isoelectric point on viral adsorption onto aquifer sediment material, we employed five different spherical bacteriophages (MS2, PRD1, Qβ, X174, and PM2) having differing isoelectric points (pI 3.9, 4.2, 5.3, 6.6, and 7.3 respectively) in laboratory viral transport studies. We employed conventional batch flowthrough columns, as well as a novel continuously recirculating column, in these studies. In a 0.78-m batch flowthrough column, the smaller phages (MS2, X174, and Qβ), which had similar diameters, exhibited maximum effluent concentration/initial concentration values that correlated exactly with their isoelectric points. In the continuously recirculating column, viral adsorption was negatively correlated with the isoelectric points of the viruses. A model of virus migration in the soil columns was created by using a one-dimensional transport model in which kinetic sorption was used. The data suggest that the isoelectric point of a virus is the predetermining factor controlling viral adsorption within aquifers. The data also suggest that when virus particles are more than 60 nm in diameter, viral dimensions become the overriding factor. 相似文献
82.
Four peptides were designed and synthesized on a highly solvating copolymer of tetraethyleneglycol diacrylate cross-linked polystyrene (PS-TTEGDA) support with very high purity and yield. The polymer was synthesized in various cross-linking densities (1, 2, 3, 4, 5 and 10%) using radical aqueous suspension polymerization. Four per cent PS-TTEGDA resin showed rigidity and mechanical characteristics comparable with those of divinylbenzene cross-linked polystyrene (PS-DVB) support. Swelling and solvation characteristics of PS-TTEGDA were much higher than PS-DVB support in all solvents used in solid-phase peptide synthesis. Forty-eight hour treatment of the support with neat trifluoroacetic acid did not show any change in its infrared spectra. PS-TTEGDA could be functionalized with chloromethyl, aminomethyl and hydroxymethyl functional groups under various controlled conditions. Synthetic utility of the support was demonstrated by the synthesis of four peptides selected from the envelope and nonstructural protein region of the prototype hepatitis C virus (HCV). These peptides were later used successfully to develop a peptide-based immunoassay (PBEIA) for the detection of HCV immunity. Peptides designed from the NS1 and NS4 protein regions were found to be very promising for the development of a new diagnostic kit to detect HCV infection in human blood. Peptide purity was tested by RP-FPLC and the peptide identity was confirmed by amino acid analysis. 相似文献
83.
Chathurika Henpita Rajesh Vyas Chastity L. Healy Tra L. Kieu Aditi U. Gurkar Matthew J. Yousefzadeh Yuxiang Cui Aiping Lu Luise A. Angelini Ryan D. O'Kelly Sara J. McGowan Sanjay Chandrasekhar Rebecca R. Vanderpool Danielle Hennessy-Wack Mark A. Ross Timothy N. Bachman Charles McTiernan Smitha P. S. Pillai Warren Ladiges Mitra Lavasani Johnny Huard Donna Beer-Stolz Claudette M. St. Croix Simon C. Watkins Paul D. Robbins Ana L. Mora Eric E. Kelley Yinsheng Wang Timothy D. O'Connell Laura J. Niedernhofer 《Aging cell》2023,22(4):e13782
Cardiomyopathy is a progressive disease of the myocardium leading to impaired contractility. Genotoxic cancer therapies are known to be potent drivers of cardiomyopathy, whereas causes of spontaneous disease remain unclear. To test the hypothesis that endogenous genotoxic stress contributes to cardiomyopathy, we deleted the DNA repair gene Ercc1 specifically in striated muscle using a floxed allele of Ercc1 and mice expressing Cre under control of the muscle-specific creatinine kinase (Ckmm) promoter or depleted systemically (Ercc1−/D mice). Ckmm-Cre+/−;Ercc1−/fl mice expired suddenly of heart disease by 7 months of age. As young adults, the hearts of Ckmm-Cre+/−;Ercc1−/fl mice were structurally and functionally normal, but by 6-months-of-age, there was significant ventricular dilation, wall thinning, interstitial fibrosis, and systolic dysfunction indicative of dilated cardiomyopathy. Cardiac tissue from the tissue-specific or systemic model showed increased apoptosis and cardiac myocytes from Ckmm-Cre+/-;Ercc1−/fl mice were hypersensitive to genotoxins, resulting in apoptosis. p53 levels and target gene expression, including several antioxidants, were increased in cardiac tissue from Ckmm-Cre+/−;Ercc1−/fl and Ercc1−/D mice. Despite this, cardiac tissue from older mutant mice showed evidence of increased oxidative stress. Genetic or pharmacologic inhibition of p53 attenuated apoptosis and improved disease markers. Similarly, overexpression of mitochondrial-targeted catalase improved disease markers. Together, these data support the conclusion that DNA damage produced endogenously can drive cardiac disease and does so mechanistically via chronic activation of p53 and increased oxidative stress, driving cardiac myocyte apoptosis, dilated cardiomyopathy, and sudden death. 相似文献
84.
Three classes of signalling molecules on B-cell membranes 总被引:1,自引:0,他引:1
R B Corley N J LoCascio M Ovnic L W Arnold P S Pillai D W Scott G Haughton 《Journal of cellular biochemistry》1985,27(1):1-12
The question of whether surface immunoglobulin and Ia molecules have a signalling function in helper T cell-dependent activation of B cells has been evaluated. Two sources of B cells have been used, one a purified population of hapten-binding B cells, the other a B-cell lymphoma, CH12, with known antigen specificity. Evidence is presented that both immunoglobulin and Ia molecules are receptors actively involved in the initial activation of resting B cells. Nevertheless, the requirements for ligand binding to either receptor can be bypassed under appropriate conditions, and the implications of this result for the function of these molecules is discussed. With respect to B-cell Ia, the authors present data that demonstrate two distinct functions of this molecule, one as a restricting element for T-cell activation, the second as a signalling receptor for B-cell excitation. On the CH12 surface, the I-A molecule fulfills the former function, but T-cell interactions with I-A fail to result in B-cell stimulation, suggesting that B-cell Ia may limit helper T cell-B cell interactions. We suggest that the binding of antigen surface immunoglobulin and binding of helper T-cell receptors to the appropriate Ia molecule(s) results in the activation of genes that encode for a third class of membrane B-cell receptors, those that bind B-cell stimulating factors. 相似文献
85.
Toxic effect of metal cations on female reproduction and gonadal functions was studied. Adult synchronized female rats were treated intraperitoneally with lead acetate and cadmium acetate separately and in combination (0.025, 0.05 and 0.1 mg/kg body wt) for 15 days. The metabolizing enzymes (17beta-hydroxy steroid oxidoreductase and UDP glucoronyl transferase) activities decreased with increasing dose showing significant change compared to control. Also, significant decrease in cytochrome P450 (CYP450) content was found after the treatment. Displacement of zinc bound to metallothionein was more in cadmium treated rats compared to other groups. In all these parameters, treatment in combination of lead and cadmium showed intermediate results indicating some kind of competition between the two metals. But the histological studies showed that combined treatment caused more cytotoxic effect than cadmium and lead alone. These results indicated that metal cations tested did have a direct inhibitory effect on metabolizing enzyme activities. 相似文献
86.
Polymerase chain reaction and gene probe detection of the 2,4-dichlorophenoxyacetic acid degradation plasmid, pJP4. 下载免费PDF全文
Specific and sensitive detection of indigenous and introduced degradative organisms is an essential prerequisite to their use in remediation of toxic waste and soil systems. Procedures were employed for the use of polymerase chain reaction and gene probes for sensitive detection of the 2,4-dichlorophenoxyacetic-acid-degrading bacterium, Alcaligenes eutrophus JMP134(pJP4). Two 20-mer oligonucleotide primers were identified for amplification of a 205-bp region of the tfdB gene of pJP4, and optimum conditions for amplification were determined. Both the polymerase chain reaction amplification process and hybridization with the 5'-end-labelled probe were found to be specific to organisms containing plasmid pJP4 or its derivative pRO103. Detection limits were determined for the template supplied either as bacterial cells or purified plasmid DNA. The detection was sensitive up to an initial inoculum of 3,000 CFU or 156 pg of total plasmid DNA. However, when the amplified product was transferred to a nylon membrane and hybridized with the 5'-end-labelled probe, the detection sensitivity increased to 300 CFU or 15.6 pg of plasmid DNA. This sensitive detection method is more specific than use of traditional indicator media (M. A. Loos, Can. J. Microbiol. 21:104-107, 1975). An oligonucleotide (20 bases) complementary to a sequence internal to the 205-bp region was synthesized and utilized as a probe to confirm the specificity of the detection. 相似文献
87.
Growth factors upregulate deposition and remodeling of ECM by endothelial cells cultured for tissue-engineering applications 总被引:1,自引:0,他引:1
Appropriate matrix formation, turnover and remodeling in tissue-engineered small diameter vascular conduits are crucial for their long-term function. The interaction between cells and extra-cellular components is indispensable in determining cellular behavior in tissues and on biomaterials. The fibrin that contains fibronectin shows promise in most aspects as a tissue engineering scaffold, whereas, deposition of elastin and collagen by endothelial cells grown in the lumen of the construct is desirable to improve post implant retention, mechanical stability and vaso-responsiveness. So far there is no report on production of extra-cellular matrix (ECM) proteins, elastin and collagen by endothelial cells (EC) in in vitro culture conditions. In this study, we have used a biomimetic approach of providing multiple growth factors (GF) in the fibronectin (FN)-containing fibrin matrix to induce production of elastin and collagen by the endothelial cells for application in vascular tissue engineering. Deposition of elastin and collagens with matrix remodeling is demonstrated through qualitative analysis of the matrices that were recovered after growing cells on the initial fibrin-FN-GF matrix. Expressions of mRNA for both proteins were assessed by real time polymerase chain reaction (RT-PCR) to estimate the effects of multiple growth factor compositions. Marked deposition of elastin and collagen was evidenced by staining the recovered matrix after different culture intervals. Obviously, the biomimetic environment created by adding angiogenic and platelet growth factors in the fibrin-fibronectin-gelatin matrix can induce deposition of collagens and elastin by EC. 相似文献
88.
Ong HK Chinna K Khoo SK Ng WL Wong BY Chow KL Chong LK Pillai K Vellayan S 《Zoo biology》2012,31(2):219-228
Logistic regression was applied to develop a morphometric sexing method of two closely related stork species that were previously sexed through amplification of the CHD gene. Tarsus length (TL) and bill length (BL) measurements were recorded from captive populations of adult Milky Stork (Mycteria cinerea) (n = 60) and Painted Stork (Mycteria leucocephala) (n = 58) at Zoo Negara Malaysia. Despite having monomorphic plumages, both stork species exhibited normal sexual size dimorphism in which males were significantly larger than females in the tested variables. Based on logistic regression analysis, BL correctly classified the sex of sampled individuals from Painted and Milky stork with an overall predicted accuracy of 94.8 and 90.0%, respectively. However, TL measurements generated a lower predicted accuracy level of 86.2% and a same accuracy level of 90% on the sex classification of individuals from Painted and Milky stork, respectively. By comparing the measurements of both species, only the average BL measurements of the Milky storks were significantly lower than that of Painted storks (t-test, P80.001). The logistic regression equation in this study may serve as a simple and more practical option for sexing Milky and Painted storks for their breeding and conservation programmes. 相似文献
89.
Kodeeswaran Paramasivam Dhas Deepa Kumar Thipramalai Thangappan Pillai Ajith Lal Kuldeep Kumar 《Ichthyological Research》2023,70(2):233-242
Ichthyological Research - Ariosoma albimaculata sp. nov. is described herein based on ten specimens [240–487 mm total length (TL)] collected from the deep-sea trawl landings at Colachel... 相似文献
90.
Jatin Machhi Navnit Prajapati Ashutosh Tripathi Zalak S. Parikh Ashish M. Kanhed Kirti Patel Prakash P. Pillai Rajani Giridhar Mange Ram Yadav 《Molecular neurobiology》2017,54(9):6697-6722
Excitotoxicty, a key pathogenic event is characteristic of the onset and development of neurodegeneration. The glutamatergic neurotransmission mediated through different glutamate receptor subtypes plays a pivotal role in the onset of excitotoxicity. The role of NMDA receptor (NMDAR), a glutamate receptor subtype, has been well established in the excitotoxicity pathogenesis. NMDAR overactivation triggers excessive calcium influx resulting in excitotoxic neuronal cell death. In the present study, a series of benzazepine derivatives, with the core structure of 3-methyltetrahydro-3H-benzazepin-2-one, were synthesised in our laboratory and their NMDAR antagonist activity was determined against NMDA-induced excitotoxicity using SH-SY5Y cells. In order to assess the multi-target-directed potential of the synthesised compounds, Aβ1–42 aggregation inhibitory activity of the most potent benzazepines was evaluated using thioflavin T (ThT) and Congo red (CR) binding assays as Aβ also imparts toxicity, at least in part, through NMDAR overactivation. Furthermore, neuroprotective, free radical scavenging, anti-oxidant and anti-apoptotic activities of the two potential test compounds (7 and 14) were evaluated using primary rat hippocampal neuronal culture against Aβ1–42-induced toxicity. Finally, in vivo neuroprotective potential of 7 and 14 was assessed using intracerebroventricular (ICV) rat model of Aβ1–42-induced toxicity. All of the synthesised benzazepines have shown significant neuroprotection against NMDA-induced excitotoxicity. The most potent compound (14) showed relatively higher affinity for the glycine binding site as compared with the glutamate binding site of NMDAR in the molecular docking studies. 7 and 14 have been shown experimentally to abrogate Aβ1–42 aggregation efficiently. Additionally, 7 and 14 showed significant neuroprotective, free radical scavenging, anti-oxidant and anti-apoptotic properties in different in vitro and in vivo experimental models. Finally, 7 and 14 attenuated Aβ1–42-induced tau phosphorylation by abrogating activation of tau kinases, i.e. MAPK and GSK-3β. Thus, the results revealed multi-target-directed potential of some of the synthesised novel benzazepines against excitotoxicity. 相似文献