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Mogher Khamaisi Allan Flyvbjerg Ziv Haramati Gadi Raz Isaiah D. Wexler Itamar Raz 《Experimental diabetes research》2002,3(4):257-264
The metabolic aberrations associated with diabetes mellitus
profoundly alter the growth hormone/insulin-like growth factor I
(GH/IGF-I) system. In severe experimental diabetes, serum IGF-I
level is reduced, reflecting altered hepatic expression. On the other
hand, increased levels of kidney IGF-I have been implicated in the
development of diabetic kidney disease. This study aimed to examine
the effect of mild experimental diabetes with hypoinsulinemia
on both the systemic and renal GH/IGF-I systems in a low-dose
streptozotocin (STZ)-induced diabetic rat. Diabetic animals with
mild hypoinsulinemia developed renal hyperfiltration within 3 days
of diabetes, whereas the renal size increased significantly only between
30 and 48 days of diabetes. Plasma GHlevels were unchanged
during the entire course of the study, but a decrease in serum
IGF-I, IGF-binding protein 3 (IGFBP-3), and IGF-binding protein
4 (IGFBP-4) occurred after 10, 30, and 48 days. Kidney IGF-I
and IGF-binding protein 1 (IGFBP-1) mRNA expression increased
after 10 and 30 days of diabetes. A significant increase in kidney
IGFBP-1/2, IGFBP-3, and IGFBP-4 proteins was seen after 48 days
of diabetes.Apositive correlations was found between renal growth
and insulin/glucose ratio (r = .57), kidney IGF-I (r = .57), IGFBP-1
mRNA(r = .43), IGFBP-1/2 (r = .41), and IGFBP-4 levels (r = .40).
These results demonstrate hyperfiltration within 3 days of diabetes
and a similar response in the IGF-I system in mildly and severely hypoinsulinemic
rats; however, renomegaly develops slower in mildly diabetic rats at least partly due to delayed changes in the renal IGF
and IGF BPs. 相似文献
64.
The major histocompatibility complex (MHC)-associated invariant chain (Ii) contains a single transmembrane domain that forms trimers. Ii is involved in the assembly of the MHC and antigen presentation, and is thus central to the function of the immune system. Here, we show by attenuated total reflectance, Fourier transform infrared (ATR-FTIR) spectroscopy that the transmembrane domain is alpha-helical and we provide a structural model of the transmembrane domain obtained by a combination of site-specific infrared dichroism and molecular dynamics (MD) simulations. This work resolves the backbone structure of a transmembrane peptide by multiple (13)C=(18)O labelling at ten different residues. A second purely computational approach, based on MD simulations of Ii transmembrane homologous sequences, yields a similar structure that is consistent with our experimental results. The structure presented forms a left-handed coiled coil with an average helix tilt of 13(+/-6) degrees; the residue Gln47 implicated in trimer formation forms strong interhelical contacts, Thr50 points to the inside of the trimeric coil and forms a network of hydrogen bonds. 相似文献
65.
Prediction of glycosylphosphatidylinositol-anchored proteins in Arabidopsis. A genomic analysis
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Glycosylphosphatidylinositol (GPI) anchoring of proteins provides a potential mechanism for targeting to the plant plasma membrane and cell wall. However, relatively few such proteins have been identified. Here, we develop a procedure for database analysis to identify GPI-anchored proteins (GAP) based on their possession of common features. In a comprehensive search of the annotated Arabidopsis genome, we identified 167 novel putative GAP in addition to the 43 previously described candidates. Many of these 210 proteins show similarity to characterized cell surface proteins. The predicted GAP include homologs of beta-1,3-glucanases (16), metallo- and aspartyl proteases (13), glycerophosphodiesterases (6), phytocyanins (25), multi-copper oxidases (2), extensins (6), plasma membrane receptors (19), and lipid-transfer-proteins (18). Classical arabinogalactan (AG) proteins (13), AG peptides (9), fasciclin-like proteins (20), COBRA and 10 homologs, and novel potential signaling peptides that we name GAPEPs (8) were also identified. A further 34 proteins of unknown function were predicted to be GPI anchored. A surprising finding was that over 40% of the proteins identified here have probable AG glycosylation modules, suggesting that AG glycosylation of cell surface proteins is widespread. This analysis shows that GPI anchoring is likely to be a major modification in plants that is used to target a specific subset of proteins to the cell surface for extracellular matrix remodeling and signaling. 相似文献
66.
By the time of diagnosis, primary neoplasms are biologically heterogeneous and contain subpopulations of cells with different metastatic potentials. The pathogenesis of a metastasis consists of many sequential steps that must be completed to produce clinically relevant lesions. During any of these steps, tumor cells interact with host factors in the microenvironment that the tumor cells can usurp. Treatment of metastasis can be directed against tumor cells and/or microenvironmental factors that support tumor growth, such as tumor-associated blood vessels. 相似文献
67.
Kearney Jennifer A. Copeland-Hardin Letonia D. Duarte Samantha Zachwieja Nicole A. Eckart-Frank Isaiah K. Hawkins Nicole A. 《Mammalian genome》2022,33(4):565-574
Mammalian Genome - Pathogenic variants in SCN1A result in a spectrum of phenotypes ranging from mild febrile seizures to Dravet syndrome, a severe infant-onset epileptic encephalopathy. Individuals... 相似文献
68.
Joyce K. Hu Jordan C. Crampton Albert Cupo Thomas Ketas Marit J. van Gils Kwinten Sliepen Steven W. de Taeye Devin Sok Gabriel Ozorowski Isaiah Deresa Robyn Stanfield Andrew B. Ward Dennis R. Burton Per Johan Klasse Rogier W. Sanders John P. Moore Shane Crotty 《Journal of virology》2015,89(20):10383-10398
69.
Evidence from human psychophysical and animal electrophysiological studies suggests that sensitivity to interaural time delay (ITD) in the modulating envelope of a high-frequency carrier can be enhanced using half-wave rectified stimuli. Recent evidence has shown potential benefits of equivalent electrical stimuli to deaf individuals with bilateral cochlear implants (CIs). In the current study we assessed the effects of envelope shape on ITD sensitivity in the primary auditory cortex of normal-hearing ferrets, and profoundly-deaf animals with bilateral CIs. In normal-hearing animals, cortical sensitivity to ITDs (±1 ms in 0.1-ms steps) was assessed in response to dichotically-presented i) sinusoidal amplitude-modulated (SAM) and ii) half-wave rectified (HWR) tones (100-ms duration; 70 dB SPL) presented at the best-frequency of the unit over a range of modulation frequencies. In separate experiments, adult ferrets were deafened with neomycin administration and bilaterally-implanted with intra-cochlear electrode arrays. Electrically-evoked auditory brainstem responses (EABRs) were recorded in response to bipolar electrical stimulation of the apical pair of electrodes with singe biphasic current pulses (40 µs per phase) over a range of current levels to measure hearing thresholds. Subsequently, we recorded cortical sensitivity to ITDs (±800 µs in 80-µs steps) within the envelope of SAM and HWR biphasic-pulse trains (40 µs per phase; 6000 pulses per second, 100-ms duration) over a range of modulation frequencies. In normal-hearing animals, nearly a third of cortical neurons were sensitive to envelope-ITDs in response to SAM tones. In deaf animals with bilateral CI, the proportion of ITD-sensitive cortical neurons was approximately a fifth in response to SAM pulse trains. In normal-hearing and deaf animals with bilateral CI the proportion of ITD sensitive units and neural sensitivity to ITDs increased in response to HWR, compared with SAM stimuli. Consequently, novel stimulation strategies based on envelope enhancement may prove beneficial to individuals with bilateral cochlear implants. 相似文献
70.
Daniel L. Gebo Nasser R. Malit Isaiah Odhiambo Nengo 《Primates; journal of primatology》2009,50(4):311-319
New early Miocene forelimb fossils have been recovered from the Songhor and Lower Kapurtay localities in southwestern Kenya.
We describe four specimens that are similar in size and functional capabilities. Their specific allocation is problematic
but these forelimb specimens must belong to either Rangwapithecus gordoni or Proconsul africanus. If these new postcranial specimens should belong to R. gordoni, on the basis of size and common dental specimens found at Songhor, they represent a new elbow complex. The morphology of
these fossils is anatomically and functionally similar to that of Proconsul. The proconsuloid elbow complex allows extensive forelimb rotations and is capable of performing arboreal quadrupedalism
and climbing activities. No suspensory adaptations are apparent. The proconsuloid elbow complex remains a good ancestral condition
for hominoid primates. 相似文献