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排序方式: 共有189条查询结果,搜索用时 31 毫秒
31.
Zificsak CA Gingrich DE Breslin HJ Dunn DD Milkiewicz KL Theroff JP Thieu TV Underiner TL Weinberg LR Aimone LD Albom MS Mason JL Saville L Husten J Angeles TS Finn JP Jan M O'Kane TM Dobrzanski P Dorsey BD 《Bioorganic & medicinal chemistry letters》2012,22(1):133-137
The elaboration of a novel scaffold for the inhibition of JAK2 and FAK kinases was targeted in order to provide a dual inhibitor that could target divergent pathways for tumor cell progression. 相似文献
32.
Paul J Coleman Karen M Brashear Cecilia A Hunt William F Hoffman John H Hutchinson Michael J Breslin Carol A McVean Ben C Askew George D Hartman Sevgi B Rodan Gideon A Rodan Chih Tai Leu Thomayant Prueksaritanont Carmen Fernandez-Metzler Bennett Ma Laura A Libby Kara M Merkle Gary L Stump Audrey A Wallace Joseph J Lynch Robert Lynch Mark E Duggan 《Bioorganic & medicinal chemistry letters》2002,12(1):31-34
Potent non-peptidic alpha(v)beta(3) antagonists have been prepared incorporating various beta-amino acids as aspartic acid mimetics. Modification of the beta-alanine 3-substituents alters the potency and physicochemical properties of these receptor antagonists and in some cases provides orally bioavailable alpha(v)beta(3) inhibitors. 相似文献
33.
Persistent nuclear ribosomal DNA sequence polymorphism in the Amelanchier agamic complex (Rosaceae) 总被引:5,自引:0,他引:5
Campbell CS; Wojciechowski MF; Baldwin BG; Alice LA; Donoghue MJ 《Molecular biology and evolution》1997,14(1):81-90
Individual plants of several Amelanchier taxa contain many polymorphic
nucleotide sites in the internal transcribed spacers (ITS) of nuclear
ribosomal DNA (nrDNA). This polymorphism is unusual because it is not
recent in origin and thus has resisted homogenization by concerted
evolution. Amelanchier ITS sequence polymorphism is hypothesized to be the
result of gene flow between two major North American clades resolved by
phylogenetic analysis of ITS sequences. Western North American species plus
A. humilis and A. sanguinea of eastern North America form one clade (A),
and the remaining eastern North American Amelanchier make up clade B. Five
eastern North American taxa are polymorphic at many of the nucleotide sites
where clades A and B have diverged and are thought to be of hybrid origin,
with A. humilis or A. sanguinea as one parent and various members of clade
B as the other parent. Morphological evidence suggests that A. humilis is
one of the parents of one of the polymorphic taxa, a microspecies that we
refer to informally as A. "erecta." Sequences of 21 cloned copies of the
ITS1- 5.8S gene-ITS2 region from one A. "erecta" individual are identical
to A. humilis sequence or to the clade B consensus sequence, or they are
apparent recombinants of A. humilis and clade B ITS repeats. Amelanchier
"erecta" and another polymorphic taxon are suspected to be relatively old
because both grow several hundred kilometers beyond the range of one of
their parents. ITS sequence polymorphisms have apparently persisted in
these two taxa perhaps because of polyploidy and/or agamospermy (asexual
seed production), which are prevalent in the genus.
相似文献
34.
V Ugalde S Walsh R T Abresch H W Bonekat E Breslin 《Journal of applied physiology》2001,91(1):395-407
Abdominal muscles are selectively active in normal subjects during stress and may increase the potential energy for inspiration by reducing the end-expiratory lung volume (EELV). We hypothesized that a similar process would occur in subjects with myotonic muscular dystrophy (MMD), but would be less effective, because of to their weakness and altered chest wall mechanics. Fine-wire electromyography (EMG) of the transversus abdominis (TA), internal oblique (IO), external oblique, and rectus abdominis was recorded in 10 MMD and 10 control subjects. EMG activity, respiratory inductive plethysmography, and gastric pressure were recorded during static pressure measurement and at increasing levels of inspiratory resistance breathing. EELV was reduced and chest wall motion was synchronous only in controls. Although the TA and IO were selectively recruited in both groups, EMG activity of the MMD group was twice that of controls at the same inspiratory pressure. In MMD subjects with mildly reduced forced vital capacity, significant differences can be seen in abdominal muscle recruitment, wall motion, work of breathing, and ventilatory parameters. 相似文献
35.
Pauline L. Martin William Breslin Meredith Rocca David Wright Joy Cavagnaro 《Birth defects research. Part B, Developmental and reproductive toxicology》2009,86(3):176-203
This report discusses the principles of developmental and reproductive toxicity (DART) testing for biopharmaceuticals. Biopharmaceuticals are large-molecular-weight proteins or peptides produced by modern biotechnology techniques incorporating genetic engineering and hybridoma technologies. The principles of DART testing for biopharmaceuticals are similar to those for small-molecule pharmaceuticals and in general follow the regulatory guidance outlined in International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) document S5(R2). However, because many biopharmaceuticals are species-specific, alternate approaches may be needed to evaluate DART potential as outlined in ICH S6. For molecules that show species-specific cross-reactivity restricted to non-human primates (NHP), some aspects of DART may require NHP testing. For biopharmaceuticals that are uniquely specific and only active on intended human targets or human and chimpanzee targets, surrogate molecules that cross-react with the more traditional rodent species may need to be developed and used for DART testing. Alternatively, genetically modified transgenic animals may also need to be considered. Surrogate molecules and transgenic animals may also be considered for DART testing even if the biopharmaceutical is active in NHPs in order to reduce the use of NHPs. Because of the unique properties of biopharmaceuticals, a case-by-case approach is needed for DART and general toxicity evaluation, which requires consideration of specific product attributes including biochemical and biophysical characteristics, pharmacological activity, and intended clinical indication. Birth Defects Res (Part B), 33:176–203, 2009. © 2009 Wiley-Liss, Inc. 相似文献
36.
Vinpocetine is a potent antioxidant and free radical scavenger. We investigated the effects of vinpocetine on torsion/detorsion (T/D) induced testicular damage, HSP-70 expression and germ cell apoptosis in rats. Sixty Wistar albino adult male rats were divided into five groups of 12. The groups comprised a control group, a sham treated group, a T/D group, a vinpocetine treated group, and a T/D plus vinpocetine treated group. The left testis of each rat was subjected to unilateral torsion followed by detorsion after 2 h. Vinpocetine was administered intraperitoneally immediately and for 10 days following detorsion. At the end of the study, the rats were sacrificed and their testes removed and processed. HSP-70 expression, apoptosis and histopathological damage scores were determined for each group. Testicular T/D caused significant increases in apoptosis and HSP-70 expression, and a significant decrease in Johnsen’s testicular biopsy scores and mean seminiferous tubule diameter. Vinpocetine ameliorated testicular histopathology and HSP-70 expression in the T/D + vinpocetine group. Consequently, vinpocetine may prevent testicular injury following testicular torsion owing to its antioxidant effects. 相似文献
37.
Ozdener MH Brand JG Spielman AI Lischka FW Teeter JH Breslin PA Rawson NE 《Chemical senses》2011,36(7):601-612
The ability to maintain human fungiform papillae cells in culture for multiple cell cycles would be of considerable utility for characterizing the molecular, regenerative, and functional properties of these unique sensory cells. Here we describe a method for enzymatically isolating human cells from fungiform papillae obtained by biopsy and maintaining them in culture for more than 7 passages (7 months) without loss of viability and while retaining many of the functional properties of acutely isolated taste cells. Cells in these cultures exhibited increases in intracellular calcium when stimulated with perceptually appropriate concentrations of several taste stimuli, indicating that at least some of the native signaling pathways were present. This system can provide a useful model for molecular studies of the proliferation, differentiation, and physiological function of human fungiform papillae cells. 相似文献
38.
Patrick MF Derkx Thomas Janzen Kim I Sørensen Jeffrey E Christensen Birgitte Stuer-Lauridsen Eric Johansen 《Microbial cell factories》2014,13(Z1):S5
The food industry is constantly striving to develop new products to fulfil the ever changing demands of consumers and the strict requirements of regulatory agencies. For foods based on microbial fermentation, this pushes the boundaries of microbial performance and requires the constant development of new starter cultures with novel properties. Since the use of ingredients in the food industry is tightly regulated and under close scrutiny by consumers, the use of recombinant DNA technology to improve microbial performance is currently not an option. As a result, the focus for improving strains for microbial fermentation is on classical strain improvement methods. Here we review the use of these techniques to improve the functionality of lactic acid bacteria starter cultures for application in industrial-scale food production. Methods will be described for improving the bacteriophage resistance of specific strains, improving their texture forming ability, increasing their tolerance to stress and modulating both the amount and identity of acids produced during fermentation. In addition, approaches to eliminating undesirable properties will be described. Techniques include random mutagenesis, directed evolution and dominant selection schemes. 相似文献
39.
40.
Charlotte Welinder G?ran B. J?nsson Christian Ingvar Lotta Lundgren Bo Baldetorp H?kan Olsson Thomas Breslin Melinda Rezeli Bo Jansson Thomas E. Fehniger Thomas Laurell Elisabet Wieslander Krzysztof Pawlowski Gy?rgy Marko-Varga 《PloS one》2014,9(10)
Globally, malignant melanoma shows a steady increase in the incidence among cancer diseases. Malignant melanoma represents a cancer type where currently no biomarker or diagnostics is available to identify disease stage, progression of disease or personalized medicine treatment. The aim of this study was to assess the tissue expression of alpha-synuclein, a protein implicated in several disease processes, in metastatic tissues from malignant melanoma patients. A targeted Selected Reaction Monitoring (SRM) assay was developed and utilized together with stable isotope labeling for the relative quantification of two target peptides of alpha-synuclein. Analysis of alpha-synuclein protein was then performed in ten metastatic tissue samples from the Lund Melanoma Biobank. The calibration curve using peak area ratio (heavy/light) versus concentration ratios showed linear regression over three orders of magnitude, for both of the selected target peptide sequences. In support of the measurements of specific protein expression levels, we also observed significant correlation between the protein and mRNA levels of alpha-synuclein in these tissues. Investigating levels of tissue alpha-synuclein may add novel aspect to biomarker development in melanoma, help to understand disease mechanisms and ultimately contribute to discriminate melanoma patients with different prognosis. 相似文献