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排序方式: 共有335条查询结果,搜索用时 109 毫秒
31.
32.
Pryor DE O'Brate A Bilcer G Díaz JF Wang Y Wang Y Kabaki M Jung MK Andreu JM Ghosh AK Giannakakou P Hamel E 《Biochemistry》2002,41(29):9109-9115
Laulimalide is a cytotoxic natural product that stabilizes microtubules. The compound enhances tubulin assembly, and laulimalide is quantitatively comparable to paclitaxel in its effects on the reaction. Laulimalide is also active in P-glycoprotein overexpressing cells, while isolaulimalide, a congener without the drug's epoxide moiety, was reported to have negligible cytotoxic and biochemical activity [Mooberry et al. (1999) Cancer Res. 59, 653-660]. We report here that laulimalide binds at a site on tubulin polymer that is distinct from the taxoid site. We found that laulimalide, while as active as paclitaxel, epothilone A, and eleutherobin in promoting the assembly of cold-stable microtubules, was unable to inhibit the binding of radiolabeled paclitaxel or of 7-O-[N-(2,7-difluoro-4'-fluoresceincarbonyl)-L-alanyl]paclitaxel, a fluorescent paclitaxel derivative, to tubulin. Confirming this observation, we demonstrated that microtubules formed in the presence of both laulimalide and paclitaxel contained near-molar quantities, relative to tubulin, of both drugs. Laulimalide was active against cell lines resistant to paclitaxel or epothilones A and B on the basis of mutations in the M40 human beta-tubulin gene. We also report that a laulimalide analogue lacking the epoxide moiety, while less active than laulimalide in biochemical and cellular systems, is probably more active than isolaulimalide. Further exploration of the role of the epoxide in the interaction of laulimalide with tubulin is therefore justified. 相似文献
33.
Nachman RJ Coast GM Douat C Fehrentz JA Kaczmarek K Zabrocki J Pryor NW Martinez J 《Peptides》2003,24(10):1615-1621
The first reported examples of C-terminal aldehyde analogs of an insect neuropeptide are described. They are hexapeptide insect kinin analogs Boc-VFFPWG-H and Fmoc-RFFPWG-H. Activity observed for these modified analogs in an in vitro insect diuretic assay confirms that the C-terminal aldehyde group is tolerated by an insect kinin receptor. The two analogs demonstrate greatly enhanced activity over standard C-terminal amide insect kinins in a larval weight gain inhibition assay in the corn earworm Helicoverpa zea. Treatment with Boc-VFFPWG-H led to significant increases in larval mortality at doses of 500pm (45%) and 5nm (67%). Boc-VFFPWG-H represents a lead analog in the development of novel, environmentally friendly pest insect management agents based on the insect kinin class of neuropeptides. 相似文献
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Xuemei Zhao Katie Southwick Helene L. Cardasis Yi Du Michael E. Lassman Dan Xie Mohamed El‐Sherbeini Wayne M. Geissler KellyAnn D. Pryor Andreas Verras Margarita Garcia‐Calvo Dong‐Ming Shen Nathan A. Yates Shirly Pinto Ronald C. Hendrickon 《Proteomics》2010,10(15):2882-2886
Prolylcarboxypeptidase (PRCP) is a serine protease that catalyzes the cleavage of C‐terminal amino acids linked to proline in peptides. It is ubiquitously expressed and is involved in regulating blood pressure, proliferation, inflammation, angiogenesis, and weight maintenance. To identify the candidate proximal target engagement markers for PRCP inhibition in the central nervous system, we profiled the peptidome of human cerebrospinal fluid to look for PRCP substrates using a MS‐based in vitro substrate profiling assay. These experiments identified a single peptide, with the sequence YPRPIHPA, as a novel substrate for PRCP in human cerebrospinal fluid. The peptide YPRPIHPA is from the extracellular portion of human endothelin B receptor‐like protein 2. 相似文献
37.
Kartchner Caverns in Benson, AZ, was opened for tourism in 1999 after a careful development protocol that was designed to
maintain predevelopment conditions. As a part of an ongoing effort to determine the impact of humans on this limestone cave,
samples were collected from cave rock surfaces along the cave trail traveled daily by tour groups (200,000 visitors year–1) and compared to samples taken from areas designated as having medium (30–40 visitors year–1) and low (2–3 visitors year–1) levels of human exposure. Samples were also taken from fiberglass moldings installed during cave development. Culturable
bacteria were recovered from these samples and 90 unique isolates were identified by using 16S rRNA polymerase chain reaction
and sequencing. Diversity generally decreased as human impact increased leading to the isolation of 32, 27, and 22 strains
from the low, medium, and high impact areas, respectively. The degree of human impact was also reflected in the phylogeny
of the isolates recovered. Although most isolates fell into one of three phyla: Actinobacteria, Firmicutes, or Proteobacteria,
the Proteobacteria were most abundant along the cave trail (77% of the isolates), while Firmicutes predominated in the low
(66%) and medium (52%) impact areas. Although the abundance of Proteobacteria along the cave trail seems to include microbes
of environmental rather than of anthropogenic origin, it is likely that their presence is a consequence of increased organic
matter availability due to lint and other organics brought in by cave visitors. Monitoring of the cave is still in progress
to determine whether these bacterial community changes may impact the future development of cave formations. 相似文献
38.
Kowalchick JE Leiting B Pryor KD Marsilio F Wu JK He H Lyons KA Eiermann GJ Petrov A Scapin G Patel RA Thornberry NA Weber AE Kim D 《Bioorganic & medicinal chemistry letters》2007,17(21):5934-5939
Various beta-amino amides containing triazolopiperazine heterocycles have been prepared and evaluated as potent, selective, orally active dipeptidyl peptidase IV (DPP-4) inhibitors. These compounds display excellent oral bioavailability and good overall pharmacokinetic profiles in preclinical species. Moreover, in vivo efficacy in an oral glucose tolerance test in lean mice is demonstrated. 相似文献
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Lysosomes: fusion and function 总被引:7,自引:0,他引:7
Lysosomes are dynamic organelles that receive and degrade macromolecules from the secretory, endocytic, autophagic and phagocytic membrane-trafficking pathways. Live-cell imaging has shown that fusion with lysosomes occurs by both transient and full fusion events, and yeast genetics and mammalian cell-free systems have identified much of the protein machinery that coordinates these fusion events. Many pathogens that hijack the endocytic pathways to enter cells have evolved mechanisms to avoid being degraded by the lysosome. However, the function of lysosomes is not restricted to protein degradation: they also fuse with the plasma membrane during cell injury, as well as having more specialized secretory functions in some cell types. 相似文献