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81.
Effects of pH and low density lipoprotein (LDL) on PCSK9-dependent LDL receptor regulation 总被引:2,自引:0,他引:2
82.
Admixture mapping of an allele affecting interleukin 6 soluble receptor and interleukin 6 levels 下载免费PDF全文
Reich D Patterson N Ramesh V De Jager PL McDonald GJ Tandon A Choy E Hu D Tamraz B Pawlikowska L Wassel-Fyr C Huntsman S Waliszewska A Rossin E Li R Garcia M Reiner A Ferrell R Cummings S Kwok PY Harris T Zmuda JM Ziv E;Health Aging Body Composition 《American journal of human genetics》2007,80(4):716-726
Circulating levels of inflammatory markers can predict cardiovascular disease risk. To identify genes influencing the levels of these markers, we genotyped 1,343 single-nucleotide polymorphisms (SNPs) in 1,184 African Americans from the Health, Aging and Body Composition (Health ABC) Study. Using admixture mapping, we found a significant association of interleukin 6 soluble receptor (IL-6 SR) with European ancestry on chromosome 1 (LOD 4.59), in a region that includes the gene for this receptor (IL-6R). Genotyping 19 SNPs showed that the effect is largely explained by an allele at 4% frequency in West Africans and at 35% frequency in European Americans, first described as associated with IL-6 SR in a Japanese cohort. We replicate this association (P<1.0x10-12) and also demonstrate a new association with circulating levels of a different molecule, IL-6 (P<3.4x10-5). After replication in 1,674 European Americans from Health ABC, the combined result is even more significant: P<1.0x10-12 for IL-6 SR, and P<2.0x10-9 for IL-6. These results also serve as an important proof of principle, showing that admixture mapping can not only coarsely localize but can also fine map a phenotypically important variant. 相似文献
83.
Pseudomonas aeruginosa infection of patients with cystic fibrosis (CF) is a leading cause of their morbidity and mortality. Pathogenesis is initiated
in part by molecular interactions of P. aeruginosa with carbohydrate residues in airway mucins that accumulate in the lungs of patients with this disease. To explore the nature
of the glycans recognized by a stable, mucoid, alginate-producing strain P. aeruginosa 8830 we generated a genetically modified Pa8830 expressing green fluorescent protein (Pa3380-GFP). We tested its binding
to a panel of glycolipids and neoglycolipids in which selected glycans were covalently attached to dipalmitoyl phosphatidylethanolamine
and analyzed on silica gel surfaces. Among all glycans tested, Pa8830-GFP bound best to sialyl-Lex-containing glycan NeuAc(α2-3)Gal(β1-4)[Fuc(α1-3)]GlcNAc-R and bound weakly to H-type blood group Fucα1-2Galβ1-4GlcNAc-R,
sialyl-lactose, and Lex, and exhibited little binding toward non-fucosylated derivatives. Interestingly, while Pa8830-GFP bound to the glycosphingolipid
asialoGM1, it did not appear to bind to a wide variety of other glycosphingolipids including GM1, GM2, asialoGM2, and sulfatide.
These results indicate that P. aeruginosa 8830 has preferential binding to sialyl-Lex-containing glycans and has weak recognition of related fucose- and sialic acid-containing glycans. The finding that Pa8830
binds sialyl-Lex-containing glycans, which occur at increased levels in mucins from CF patients, is consistent with studies of other strains
of P. aeruginosa and further suggests that such glycans on CF mucins contribute to disease pathogenesis.
Invited Submission from Dr. Subhash Basu, from the 7th International Symposium on Biochemical Roles of Eukaryotic Cell Surface
Macromolecules in Puri, India, January, 2005. 相似文献
84.
The ex situ population of maned wolves is not self‐sustaining due to poor reproduction, caused primarily by parental incompetence. Studies have shown that environmental enrichment can promote natural parental behaviors in zoo animals. The objective of this study was to determine the effects of environmental enrichment on behavioral and physiological responses of maned wolves. During an 8‐week experimental period, daily behavior observations and fecal sample collection were conducted on four adult wolves (2.2) individually housed in environments without enrichment. After 2 weeks, the wolves were chronologically provided with 2‐week intervals of hiding dead mice around the exhibit, no enrichment, and introduction of boomer balls. Responses of the wolves to enrichment were assessed based on activity levels and exploratory rates, as well as the level of corticoid metabolites in fecal samples collected daily throughout the study period. Providing wolves with environmental enrichment significantly increased exploratory behaviors (P<0.05), especially when mice were hidden in the enclosure. Fecal corticoid concentrations were increased during periods of enrichment in males (P<0.05), but not in females. Overall, there were no correlations between behavioral responses to enrichment and fecal corticoid levels. Behavioral results suggest that environmental enrichment elicits positive effects on the behavior of captive maned wolves. There is evidence suggesting that providing animals with ability to forage for food is a more effective enrichment strategy than introducing objects. There is need for a longer term study to determine the impact of environmental enrichment in this species. Zoo Biol 26:331–343, 2007. © 2007 Wiley‐Liss, Inc. 相似文献
85.
Cao Yong Hinz Leon Taylor Christopher A. Metzke Brian Cummings Kevin S. 《Hydrobiologia》2022,849(9):2193-2208
Hydrobiologia - Fish hosts are critical for freshwater mussels. However, correlation between mussel and fish species richness (SR) is variable. Here, we examine how the environment affects this... 相似文献
86.
Lullfitz Alison Knapp Lynette Cummings Shandell Hopper Stephen D. 《Plant and Soil》2022,476(1-2):589-625
Plant and Soil - Underground storage organs (USOs) have long featured prominently in human diets. They are reliable year-round resources, especially valuable in seasonal climates. We... 相似文献
87.
Song X Lasanajak Y Xia B Heimburg-Molinaro J Rhea JM Ju H Zhao C Molinaro RJ Cummings RD Smith DF 《Nature methods》2011,8(1):85-90
Major challenges of glycomics are to characterize a glycome and identify functional glycans as ligands for glycan-binding proteins (GBPs). To address these issues we developed a general strategy termed shotgun glycomics. We focus on glycosphingolipids (GSLs), a class of glycoconjugates that is challenging to study, recognized by toxins, antibodies and GBPs. We derivatized GSLs extracted from cells with a heterobifunctional fluorescent tag suitable for covalent immobilization. We separated fluorescent GSLs by multidimensional chromatography, quantified them and coupled them to glass slides to create GSL shotgun microarrays. Then we interrogated the microarrays with cholera toxin, antibodies and sera from individuals with Lyme disease to identify biologically relevant GSLs that we subsequently characterized by mass spectrometry. Shotgun glycomics incorporating GSLs and potentially glycoprotein-derived glycans is an approach for accessing the complex glycomes of animal cells and is a strategy for focusing structural analyses on functionally important glycans. 相似文献
88.
Ningyan Zhang Liming Liu Calin Dan Dumitru Nga Rewa Houston Cummings Michael Cukan Youwei Jiang Yuan Li Fang Li Teresa Mitchell Muralidhar R Mallem Yangsi Ou Rohan N Patel Kim Vo Hui Wang Irina Burnina Byung-Kwon Choi Hans Huber Terrance A Stadheim Dongxing Zha 《MABS-AUSTIN》2011,3(3):289-298
Mammalian cell culture systems are used predominantly for the production of therapeutic monoclonal antibody (mAb) products. A number of alternative platforms, such as Pichia engineered with a humanized N-linked glycosylation pathway, have recently been developed for the production of mAbs. The glycosylation profiles of mAbs produced in glycoengineered Pichia are similar to those of mAbs produced in mammalian systems. This report presents for the first time the comprehensive characterization of an anti-human epidermal growth factor receptor 2 (HER2) mAb produced in glycoengineered Pichia, and a study comparing the anti-HER2 from Pichia, which had an amino acid sequence identical to trastuzumab, with trastuzumab. The comparative study covered a full spectrum of preclinical evaluation, including bioanalytical characterization, in vitro biological functions, in vivo anti-tumor efficacy and pharmacokinetics in both mice and non-human primates. Cell signaling and proliferation assays showed that anti-HER2 from Pichia had antagonist activities comparable to trastuzumab. However, Pichia-produced material showed a 5-fold increase in binding affinity to FcγIIIA and significantly enhanced antibody dependent cell-mediated cytotoxicity (ADCC) activity, presumably due to the lack of fucose on N-glycans. In a breast cancer xenograft mouse model, anti-HER2 was comparable to trastuzumab in tumor growth inhibition. Furthermore, comparable pharmacokinetic profiles were observed for anti-HER2 and trastuzumab in both mice and cynomolgus monkeys. We conclude that glycoengineered Pichia provides an alternative production platform for therapeutic mAbs and may be of particular interest for production of antibodies for which ADCC is part of the clinical mechanism of action.Key words: glycoengineered Pichia, anti-HER2, trastuzumab, xenograft, PK, ADCC 相似文献
89.
Shrirang Karve Michael E. Werner Natalie D. Cummings Rohit Sukumar Edina C. Wang Ying-Ao Zhang Andrew Z. Wang 《Journal of visualized experiments : JoVE》2011,(55)
Nanotechnology is a relatively new branch of science that involves harnessing the unique properties of particles that are nanometers in scale (nanoparticles). Nanoparticles can be engineered in a precise fashion where their size, composition and surface chemistry can be carefully controlled. This enables unprecedented freedom to modify some of the fundamental properties of their cargo, such as solubility, diffusivity, biodistribution, release characteristics and immunogenicity. Since their inception, nanoparticles have been utilized in many areas of science and medicine, including drug delivery, imaging, and cell biology1-4. However, it has not been fully utilized outside of "nanotechnology laboratories" due to perceived technical barrier. In this article, we describe a simple method to synthesize a polymer based nanoparticle platform that has a wide range of potential applications. The first step is to synthesize a diblock co-polymer that has both a hydrophobic domain and hydrophilic domain. Using PLGA and PEG as model polymers, we described a conjugation reaction using EDC/NHS chemistry5 (Fig 1). We also discuss the polymer purification process. The synthesized diblock co-polymer can self-assemble into nanoparticles in the nanoprecipitation process through hydrophobic-hydrophilic interactions.The described polymer nanoparticle is very versatile. The hydrophobic core of the nanoparticle can be utilized to carry poorly soluble drugs for drug delivery experiments6. Furthermore, the nanoparticles can overcome the problem of toxic solvents for poorly soluble molecular biology reagents, such as wortmannin, which requires a solvent like DMSO. However, DMSO can be toxic to cells and interfere with the experiment. These poorly soluble drugs and reagents can be effectively delivered using polymer nanoparticles with minimal toxicity. Polymer nanoparticles can also be loaded with fluorescent dye and utilized for intracellular trafficking studies. Lastly, these polymer nanoparticles can be conjugated to targeting ligands through surface PEG. Such targeted nanoparticles can be utilized to label specific epitopes on or in cells7-10.Download video file.(41M, mov) 相似文献
90.