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排序方式: 共有350条查询结果,搜索用时 15 毫秒
241.
Nusz DJ White DC Dai Q Pippen AM Thompson MA Walton GB Parsa CJ Koch WJ Annex BH 《American journal of physiology. Heart and circulatory physiology》2003,285(4):H1554-H1562
A decrease in vascular density in peripheral skeletal muscle has been associated with exercise intolerance in humans with congestive heart failure (CHF). The purpose of this study was to determine whether CHF results in a reduction in vascular density in peripheral skeletal muscle. In this established model, CHF was induced by coronary artery ligation in New Zealand White rabbits and sham rabbits that underwent an identical surgical procedure without ligation of the coronary artery. At study termination, rabbits underwent hemodynamic testing and skeletal muscle analysis. The first series of rabbits was divided into sham (n = 6) and CHF (n = 6) 21 days postoperatively. Ten CHF rabbits were then examined 3 (n = 3), 7 (n = 3), and 14 days (n = 4) postoperatively. Vascular density in sham tibialis anterior muscle was 347 +/- 41 capillaries/mm2 or 1.20 +/- 0.11 capillaries/muscle fiber. In 21-day CHF rabbits, the capillary density was significantly lower, 236 +/- 14 capillaries/mm2 or 0.84 +/- 0.04 capillaries/muscle fiber (both P < 0.00001 vs. sham); PECAM protein was 2-fold lower (P < 0.0001) in muscle protein lysates; the fraction of apoptotic cells was greater, 3.8 +/- 2.2 vs. 0.69 +/- 0.56 (P < 0.02 vs. sham) with many TdT-mediated dUTP-biotin nick-end labeling-positive endothelial cells; and Bax protein was 2.8-fold greater (P < 0.0001). By regression analysis, vascular density tended to decrease over time (r2 = 0.572, P < 0.0001). Vascular rarefaction and endothelial apoptosis develop after experimental CHF and may contribute to the skeletal muscle abnormalities in this disease. Modulating vascular density may provide new approaches to treat exercise intolerance in CHF. 相似文献
242.
Critical role for mouse Hus1 in an S-phase DNA damage cell cycle checkpoint 总被引:8,自引:0,他引:8
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Mouse Hus1 encodes an evolutionarily conserved DNA damage response protein. In this study we examined how targeted deletion of Hus1 affects cell cycle checkpoint responses to genotoxic stress. Unlike hus1(-) fission yeast (Schizosaccharomyces pombe) cells, which are defective for the G(2)/M DNA damage checkpoint, Hus1-null mouse cells did not inappropriately enter mitosis following genotoxin treatment. However, Hus1-deficient cells displayed a striking S-phase DNA damage checkpoint defect. Whereas wild-type cells transiently repressed DNA replication in response to benzo(a)pyrene dihydrodiol epoxide (BPDE), a genotoxin that causes bulky DNA adducts, Hus1-null cells maintained relatively high levels of DNA synthesis following treatment with this agent. However, when treated with DNA strand break-inducing agents such as ionizing radiation (IR), Hus1-deficient cells showed intact S-phase checkpoint responses. Conversely, checkpoint-mediated inhibition of DNA synthesis in response to BPDE did not require NBS1, a component of the IR-responsive S-phase checkpoint pathway. Taken together, these results demonstrate that Hus1 is required specifically for one of two separable mammalian checkpoint pathways that respond to distinct forms of genome damage during S phase. 相似文献
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245.
Parsa CJ Reed RC Walton GB Pascal LS Thompson RB Petrofski JA Emani SM Folgar F Riel RU Nicchitta CV Koch WJ 《The journal of gene medicine》2005,7(5):595-603
BACKGROUND: Recent studies suggest that gene therapy using replication-deficient adenoviruses will benefit treatment of cardiovascular diseases including heart failure. A persistent hurdle is the effective and reproducible delivery of a transgene to the myocardium with minimal iatrogenic morbidity. In this study, we sought to design a relatively non-invasive percutaneous gene delivery system that would maximize cardiac transgene expression and minimize mortality after intracoronary adenovirus injection. METHODS: Adult rabbits received a left circumflex coronary artery (LCx) infusion of 5x10(11) total viral particles of an adenovirus containing the marker transgene beta-galactosidase (Adeno-betaGal) via either a continuous infusion method utilizing an oxygenated, normothermic, physiologic pH Krebs solution driven by a Langendorff apparatus (n=12) or a timed bolus and set concentration at a constant infusion rate to the LCx (n=12). Six rabbits underwent global transgene delivery via an invasive method involving intraventricular delivery and aortic root cross-clamping. The efficacy of transgene expression via these three distinct delivery methods was determined in the left ventricle at 5 days by histological staining and colorimetric quantification assay. RESULTS: While the open-chest, aortic cross-clamping method provides the highest level of gene expression throughout the heart, the morbidity of this procedure is clinically prohibitive. Percutaneous LCx delivery of Adeno-betaGal using the Langendorff apparatus was associated with the lowest morbidity and mortality while still supporting significant myocardial gene expression. CONCLUSIONS: Percutaneous delivery of an adenovirus solution using a continuous infusion of oxygenated Krebs solution via a Langendorff apparatus appears to be a gene delivery modality offering the best compromise of gene expression and clinical utility to maximize any potential therapeutic outcome. 相似文献
246.
We describe the results of a clonal analysis of spinal cord development in the zebrafish. The data were obtained from embryos
in which fluorescent lineage tracer was injected into single cells in the neural plate at the two-somite stage. Injected animals
were allowed to survive until either 4 days or 2 weeks postfertilization. In other experiments, bromodeoxy uridine (BrdU)
was injected intraperitoneally at 30 h postfertilization (hpf) after lineage tracer injection in the neural plate at the two-somite
stage, and the embryos fixed at 38 hpf. We restricted our experiments to the thoracic region of the spinal cord. Our experiments
were aimed at answering questions regarding the proliferative abilities of neuroepithelial cells during embryonic development
(as deduced from the size of the clones), the modes of cell division (as deduced from the uptake of BrdU into clone cells),
positional differences in the proliferation of cells within the neural plate itself, the cellular composition of the clones,
and cell dispersion (deduced from the regional distribution of clone cells).
Received: 30 December 1994 / Accepted: 9 March 1997 相似文献
247.
The effects of bisabolangelone on the development of codling moth larvae,Cydia pomonella L., and on ovipositional behaviour of the females were studied under laboratory conditions. Entry of the neonate larvae into
apples and their development on a semi-synthetic medium were completely inhibited when the larvae were exposed respectively
to 10 μg a.i./cm2 and 20 μg a.i./ml of this compound. While concentrations of 1.25 to 5.0 μg a.i./ml bisabolangelone in the medium did not
significantly affect larval development, exposure of the larvae to a higher rate (10 μg a.i./ml) resulted in 80% mortality
during the first week. Nevertheless, the larvae which survived the treatments underwent further development until emergence
of the adults. No significant changes in duration of larval or pupal periods were recorded.
Oviposition of the females in plastic beakers, whose inner surfaces were partially painted with two concentrations of bisabolangelone
(1.25 to 5.0 μg a.i./cm2), was significantly reduced and the eggs were mainly laid on the parts painted with the ethanol solvent alone. When the inner
surface of the cups was completely treated (i.e. top, bottom, and side) with similar concentrations of bisabolangelone, a
dramatic reduction in oviposition occurred and the eggs were mostly laid on the bottom of the beakers. While this compound
did not significantly influence egg hatch, it inhibited the normal upward movement of the adults in the cups and migration
of the newly hatched larvae through perforations of the lids. 相似文献
248.
Paul W. Cook Deborah Damm Brett L. Garrick Kathleen M. Wood Cyrus E. Karkaria Shigeki Higashiyama Michael Klagsbrun Judith A. Abraham 《Journal of cellular physiology》1995,163(2):407-417
Previous studies have indicated that heparin differentially regulates heparin-binding EGF-like growth factor (HB-EGF) and amphiregulin (AR) mitogenic activity. To further explore this phenomenon, these mitogens were compared under identical cell culture conditions in two different assays. The results of our present investigation demonstrated that AR-mediated mitogenic activity in the murine AKR-2B fibroblast-like cell line was inhibited by heparin, while HB-EGF activity was enhanced. However, the absolute effect of heparin appeared to be cell type specific since HB-EGF mitogenic activity was not dramatically affected by coincubation with heparin when tested on human dermal fibroblasts. Several studies have indicated that mutation of a conserved leucine in the carboxyl-terminal region of both EGF and transforming growth factor-α results in decreased affinity for EGF receptors. Since this leucine is present in the analogous position of HB-EGF, but absent in AR, we examined the effect of deleting this residue by carboxyl-terminal truncation of HB-EGF. Analysis of recombinant forms of HB-EGF demonstrated that HB-EGF can be converted to a heparin-inhibited growth factor if the putative mature form of the protein is truncated by two residues (leucine76 and proline77) at the carboxyl terminus. Further analysis demonstrated that only leucine76 appears to be required for heparin-dependent enhancement of HB-EGF-mediated mitogenic activity, indicating that this amino acid may play a pivotal role in controlling the response of HB-EGF to heparin or related glycosaminoglycan sulfates. Our results also suggest that expression of different HB-EGF forms in vivo could result in the production of HB-EGFs with divergent responses to sulfated glycosaminoglycans and proteoglycans. © 1995 Wiley-Liss, Inc. 相似文献
249.
Nicole Azer Nicholas Trunfio Erica J. Fratz-Berilla Jin Sung Hong Jackie Cullinan Talia Faison Cyrus D. Agarabi David N. Powers 《Biotechnology progress》2023,39(4):e3347
Bioreactor parameters can have significant effects on the quantity and quality of biotherapeutics. Monoclonal antibody products have one particularly important critical quality attribute being the distribution of product glycoforms. N-linked glycosylation affects the therapeutic properties of the antibody including effector function, immunogenicity, stability, and clearance rate. Our past work revealed that feeding different amino acids to bioreactors altered the productivity and glycan profiles. To facilitate real-time analysis of bioreactor parameters and the glycosylation of antibody products, we developed an on-line system to pull cell-free samples directly from the bioreactors, chemically process them, and deliver them to a chromatography-mass spectroscopy system for rapid identification and quantification. We were able to successfully monitor amino acid concentration on-line within multiple reactors, evaluate glycans off-line, and extract four principal components to assess the amino acid concentration and glycosylation profile relationship. We found that about a third of the variability in the glycosylation data can be predicted from the amino acid concentration. Additionally, we determined that the third and fourth principal component accounts for 72% of our model's predictive power, with the third component indicated to be positively correlated with latent metabolic processes related to galactosylation. Here we present our work on rapid online spent media amino acid analysis and use the determined trends to collate with glycan time progression, further elucidating the correlation between bioreactor parameters such as amino acid nutrient profiles, and product quality. We believe such approaches may be useful for maximizing efficiency and reducing production costs for biotherapeutics. 相似文献
250.
Analysis of the pattern of residue to residue contacts at the interface of 50 helix to helix packings observed in ten proteins of known structure supports a model for helix to helix packing in which the ridges and grooves on the helix surface intercalate. These ridges are formed by rows of residues whose separation in sequence is usually four, occasionally three and rarely one. The model explains the observed predominance of packings whose interhelical angle is ~ ?50 °. Of the 50 packings, 38 agree with the model and the general features of another ten packings are described by an extension to the model in which ridges can pack across each other if a small side-chain occurs at the place where they cross. 相似文献