全文获取类型
收费全文 | 469篇 |
免费 | 49篇 |
出版年
2021年 | 6篇 |
2018年 | 4篇 |
2016年 | 7篇 |
2015年 | 11篇 |
2014年 | 15篇 |
2013年 | 20篇 |
2012年 | 19篇 |
2011年 | 20篇 |
2010年 | 11篇 |
2009年 | 14篇 |
2008年 | 23篇 |
2007年 | 23篇 |
2006年 | 23篇 |
2005年 | 18篇 |
2004年 | 24篇 |
2003年 | 19篇 |
2002年 | 13篇 |
2001年 | 18篇 |
2000年 | 14篇 |
1999年 | 13篇 |
1998年 | 5篇 |
1997年 | 3篇 |
1996年 | 3篇 |
1995年 | 9篇 |
1994年 | 4篇 |
1993年 | 4篇 |
1992年 | 14篇 |
1991年 | 9篇 |
1990年 | 8篇 |
1989年 | 4篇 |
1988年 | 8篇 |
1987年 | 6篇 |
1986年 | 6篇 |
1985年 | 13篇 |
1984年 | 11篇 |
1983年 | 8篇 |
1982年 | 5篇 |
1981年 | 4篇 |
1980年 | 7篇 |
1979年 | 4篇 |
1978年 | 3篇 |
1977年 | 6篇 |
1976年 | 7篇 |
1975年 | 4篇 |
1974年 | 7篇 |
1973年 | 5篇 |
1972年 | 3篇 |
1971年 | 4篇 |
1970年 | 4篇 |
1968年 | 3篇 |
排序方式: 共有518条查询结果,搜索用时 26 毫秒
31.
Highly active fluorescent compounds having kappa opioid activity were identified following the screening in a kappa-specific radioligand binding assay of a positional scanning tetrapeptide combinatorial library in which every tetrapeptide was fluorescently labeled. Lissamine rhodamine B sulfonyl chloride was coupled to the N terminal of a mixture-based tetrapeptide positional scanning library made up of over 7.3 million tetrapeptides. Upon determination of the most active mixtures for each position of the library in the kappa binding assay, individual rhodamine labeled tetrapeptides were then synthesized and tested to determine their activities. Eight individual rhodamine labeled peptides were identified that were specific for the kappa opioid receptor, having binding affinities ranging from 5-20 nM. These peptides were poor inhibitors at the mu and delta receptors (K(i)>5,000 nM). Furthermore, neither rhodamine itself nor these same tetrapeptides lacking the N-terminal rhodamine had any significant activity at the kappa receptor, indicating that both the tetrapeptide sequence and the rhodamine moiety are required for receptor binding. This study has demonstrated that novel fluorescent compounds with intrinsic activity can be identified through the use of combinatorial chemistry. 相似文献
32.
Friedrich G Appel K Rose T Wangemann M Althaus M Rissler K 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2004,808(2):131-139
A rapid and sensitive assay for the determination of dihydroergocryptine (DHEC) in human plasma and urine samples with dihydroergotamine (DHET) as the internal standard was developed. The procedure employs on-line sample preparation using an extraction pre-column and an octadecylsilylsilica (ODS) analytical column. After centrifugation human plasma or urine were injected onto the pre-column, concentrated and extracted, back-flushed onto the analytical column and eluted with a binary methanol--aqueous formic acid gradient. Either determination of DHEC as well of its mono- and dihydroxy-metabolites was performed by measurement of the signal responses from MS detection in the selected reaction monitoring (SRM) mode using the transition of the respective parent ions to the common daughter ion at m/z=270.2 amu. The limit of quantitation (LOQ) for determinations of DHEC in both plasma and urine were 25 pg/ml for injected sample volumes of 400 microl. Proportionality of signal responses versus concentration was accomplished within the range of 25-1000 pg/ml. Recovery of target analyte from plasma was 99%. Mean values of the coefficients of variation (CV) for the target analyte in plasma ranged from 1.7 to 13.8% (within-day) and 5.0 to 9.1% (between-day) and accuracy from 91.7 to 102.6% for the within-day and from 95.8 to 98.8% for the between-day measurements. The corresponding values for determinations in urine were 1.7-14.5% (within-day) and 5.3-11.8% (between-day) for CV and 95.8-110.7% (within-day) and 100.1-104.6% (between-day) for accuracy. 相似文献
33.
Gasteiger E Gattiker A Hoogland C Ivanyi I Appel RD Bairoch A 《Nucleic acids research》2003,31(13):3784-3788
The ExPASy (the Expert Protein Analysis System) World Wide Web server (http://www.expasy.org), is provided as a service to the life science community by a multidisciplinary team at the Swiss Institute of Bioinformatics (SIB). It provides access to a variety of databases and analytical tools dedicated to proteins and proteomics. ExPASy databases include SWISS-PROT and TrEMBL, SWISS-2DPAGE, PROSITE, ENZYME and the SWISS-MODEL repository. Analysis tools are available for specific tasks relevant to proteomics, similarity searches, pattern and profile searches, post-translational modification prediction, topology prediction, primary, secondary and tertiary structure analysis and sequence alignment. These databases and tools are tightly interlinked: a special emphasis is placed on integration of database entries with related resources developed at the SIB and elsewhere, and the proteomics tools have been designed to read the annotations in SWISS-PROT in order to enhance their predictions. ExPASy started to operate in 1993, as the first WWW server in the field of life sciences. In addition to the main site in Switzerland, seven mirror sites in different continents currently serve the user community. 相似文献
34.
35.
36.
37.
The development of high throughput utilities to identify proteins is a major challenge in present research in the field of proteomics. One such utility, the molecular scanner, uses proteins separated by two-dimensional polyacrylamide gel electrophoresis that are digested in the gel and during transfer onto a collecting membrane. After adding a matrix, the membrane is inserted into a matrix-assisted laser desorption/ionization-time of flight mass spectrometer and a peptide mass fingerprint (PMF) is measured for every scanned site. Since the spacing between scanned sites is much smaller than the size of the most abundant protein spots, there is a certain redundancy in the data that was used in an earlier experiment with Escherichia coli [1] to improve mass calibration and PMF identification results. It was observed that the signal intensity of a peptide mass as a function of the position on the membrane showed similar patterns if peptides stemmed from the same protein. Taking account of these similarities a clustering algorithm was used to find lists of experimental masses with similar intensity distributions, which provided clearer identification of the corresponding proteins. Here, these methods are applied to a human plasma scan, where proteins were highly modified and less separated. The presence of very abundant proteins like albumin and immunoglobulins added another difficulty. The calibration of the initial PMFs was not satisfactory and masses had to be recalibrated. After discarding chemical noise, the membrane was partitioned into regions and for each region protein identification was carried out separately. A new scoring method was used, where the PMF score was multiplied by a factor that measures the similarity of matching peptides. This method proved to be more robust than the method developed in [1] if the region where a protein was found had an extended, nonspherical shape and strong overlap with regions of other proteins. Many proteins annotated on the SWISS-2D PAGE human plasma master gel could be clearly identified and many interesting properties were observed. 相似文献
38.
39.
Appropriate particle size may be a critical characteristic for effective granular ant baits. We examined the particle size preference of six species of pest ants to an anchovy-based bait. We also examined head capsule widths of Argentine ants, Linepithema humile (Mayr) (mean = 0.54 mm), California harvester ants, Pogonomyrmex californicus (Buckley) (mean = 1.63 mm), red imported fire ants, Solenopsis invicta Buren (mean = 0.9 mm), and southern fire ants, Solenopsis xyloni McCook (mean = 0.76 mm) and compared them with the first and second most preferred particle size. There were differences between particle size of which the most mass was removed and of which there were more particles removed by ants. California Argentine ants, southern fire ants, and Alabama Argentine ants removed more 840 to 1,000-microm particle mass of the anchovy diet but had more visits to dishes containing 420 to 590 microm particles. California harvester ants and Allegheny mound ants, Formica spp., removed more >2,000 microm particle mass but visited dishes containing 1,000 to 2,000 microm particles more often. Red imported fire ants also removed more >2,000 microm particle mass but visited dishes with 590 to 840-microm particles most often. Pharaoh ants, Monomorium pharaonis (L.), removed and visited 420 to 590-microm particles more than any other size. A linear regression model determined that particle size preferred by each ant species relates to forager head width. The majority of particles of commercial ant bait, including Amdro, Ascend, Award, Bushwhacker, Max Force with fipronil, and old and new formulations of Max Force with hydramethylnon, were 1,000 to 2,000 microm, but the majority of Niban particles were <420 microm. Altering the size of particles of toxic ant baits to fit the particle size preference of each pest ant species may increase the efficacy of ant baits. 相似文献
40.
Turgeon NA Banuelos SJ Shultz LD Lyons BL Iwakoshi N Greiner DL Mordes JP Rossini AA Appel MC 《Experimental biology and medicine (Maywood, N.J.)》2003,228(9):1096-1104
Small animal models with the capacity to support engraftment of a functional human immune system are needed to facilitate studies of human alloimmunity. In the present investigation, non-obese diabetic (NOD) severe combined immunodeficient (scid) beta2-microglobulin-null (B2mnull) mice engrafted with human peripheral blood lymphocytes (hu-PBL-NOD-scid B2mnull mice) were used as in vivo models for studying human skin allograft rejection. Hu-PBL-NOD-scid B2mnull mice were established by injection of human spleen cells or PBLs and transplanted with full-thickness allogeneic human skin. Human cell engraftment was enhanced by injection of anti-mouse CD122 antibody. The respective contributions of human CD4+ and CD8+ cells in allograft rejection were determined using depleting antibodies. Human skin grafts on unmanipulated NOD-scid B2mnull mice uniformly survived but on chimeric hu-PBL-NOD-scid B2mnull mice exhibited severe immune-mediated injury that often progressed to complete rejection. The alloaggressive hu-PBLs did not require prior in vitro sensitization to elicit targeted effector cell activity. Extensive mononuclear cell infiltration directed towards human-origin endothelium was associated with thrombosis and fibrin necrosis. No evidence of graft-versus-host disease was detected. Either CD4+ or CD8+ T cells may mediate injury and alloimmune rejection of human skin grafts on hu-PBL-NOD-scid B2mnull mice. It is proposed that Hu-PBL-NOD-scid B2mnull mice engrafted with human skin will provide a useful model for analysis of interventions designed to modulate human allograft rejection. 相似文献