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41.
Kozic D Medic-Stojanoska M Ostojic J Popovic L Vuckovic N 《Neuro endocrinology letters》2007,28(5):560-564
MR spectroscopy (MRS) of hormonally active pituitary adenomas has not been published in literature. We report MR imaging and spectroscopy findings in a 41-year-old man with extrapituitary growth hormone-secreting adenoma. Application of the single voxel proton MRS, SE 135 technique, with voxel size 11x11x11 mm, revealed the elevated choline peak (resonance at 3.2 ppm) in the paramedial aspect of the tumor, while no metabolic activity in the mentioned region was noted using the same method 11 months after Lanreotide treatment. Elevation of choline peak in functional pituitary adenomas could represent an active marker of cellular proliferation, compatible with increased hormonal activity. 相似文献
42.
43.
Molecular and cellular requirements for enhanced antigen cross-presentation to CD8 cytotoxic T lymphocytes 总被引:1,自引:0,他引:1
Oizumi S Strbo N Pahwa S Deyev V Podack ER 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(4):2310-2317
MHC class I-mediated cross-priming of CD8 T cells by APCs is critical for CTL-based immunity to viral infections and tumors. We have shown previously that tumor-secreted heat shock protein gp96-chaperoned peptides cross prime CD8 CTL that are specific for genuine tumor Ags and for the surrogate Ag OVA. We now show that tumor-secreted heat shock protein gp96-chaperoned peptides enhance the efficiency of Ag cross-priming of CD8 CTL by several million-fold over the cross-priming activity of unchaperoned protein alone. Gp96 also acts as adjuvant for cross-priming by unchaperoned proteins, but in this capacity gp96 is 1000-fold less active than as a peptide chaperone. Mechanistically, the in situ secretion of gp96-Ig by transfected tumor cells recruits and activates dendritic cells and NK cells to the site of gp96 release and promotes CD8 CTL expansion locally. Gp96-mediated cross-priming of CD8 T cells requires B7.1/2 costimulation but proceeds unimpeded in lymph node-deficient mice, in the absence of NKT and CD4 cells and without CD40L. Gp96-driven MHC I cross-priming of CD8 CTL in the absence of lymph nodes provides a novel mechanism for local, tissue-based CTL generation at the site of gp96 release. This pathway may constitute a critically important, early detection, and rapid response mechanism that is operative in parenchymal tissues for effective defense against tissue damaging antigenic agents. 相似文献
44.
Electrochemical real-time monitoring of ligand binding to an engineered opioid receptor specific for morphine is reported. In the particular systems studied, 90% of the binding was found to be completed after only 85-120 s. Thus, the binding kinetics has proven to be more rapid than previously believed. The observed association rate constant for the morphine binding reaction was calculated to be 215 M(-1)s(-1). A theoretical analysis of the experimental binding data suggested that the binding sites of the engineered opioid receptor could best be described by a model having two populations of binding sites: K(D)=40 microM (13 micromol/g) and K(D)=205 microM (29 micromol/g). Furthermore, a theoretical model was developed in order to explain the observed binding of the engineered opioid receptor. This model suggested that the binding sites on the polymer surface are up to 5.1A deep and they allow 100% of the ligand (morphine) to anchor itself into the site. The predicted theoretical maximum binding capacity for the reported receptor is calculated to be approximately 2 mmol/g polymer (based on an increase of cavity density). 相似文献
45.
Selective observation of the disordered import signal of a globular protein by in-cell NMR: The example of frataxins 总被引:1,自引:0,他引:1 下载免费PDF全文
Matija Popovic Domenico Sanfelice Chiara Pastore Filippo Prischi Piero Andrea Temussi Annalisa Pastore 《Protein science : a publication of the Protein Society》2015,24(6):996-1003
We have exploited the capability of in-cell NMR to selectively observe flexible regions within folded proteins to carry out a comparative study of two members of the highly conserved frataxin family which are found both in prokaryotes and in eukaryotes. They all contain a globular domain which shares more than 50% identity, which in eukaryotes is preceded by an N-terminal tail containing the mitochondrial import signal. We demonstrate that the NMR spectrum of the bacterial ortholog CyaY cannot be observed in the homologous E. coli system, although it becomes fully observable as soon as the cells are lysed. This behavior has been observed for several other compact globular proteins as seems to be the rule rather than the exception. The NMR spectrum of the yeast ortholog Yfh1 contains instead visible signals from the protein. We demonstrate that they correspond to the flexible N-terminal tail indicating that this is flexible and unfolded. This flexibility of the N-terminus agrees with previous studies of human frataxin, despite the extensive sequence diversity of this region in the two proteins. Interestingly, the residues that we observe in in-cell experiments are not visible in the crystal structure of a Yfh1 mutant designed to destabilize the first helix. More importantly, our results show that, in cell, the protein is predominantly present not as an aggregate but as a monomeric species. 相似文献
46.
Singh N Pandey SK Anand N Dwivedi R Singh S Sinha SK Chaturvedi V Jaiswal N Srivastava AK Shah P Siddiqui MI Tripathi RP 《Bioorganic & medicinal chemistry letters》2011,21(15):4404-4408
An economical and efficient one step synthesis of a series of 8-(arylidene)-4-(aryl)-5,6,7,8-tetrahydro-quinazolin-2-ylamines and 9-(arylidene)-4-(aryl)-6,7,8,9-tetrahydro-5H-cycloheptapyrimidin-2-ylamines by the reaction of bis-benzylidene cycloalkanones and guanidine hydrochloride in presence of NaH has been developed. All the synthesized compounds were evaluated against Mycobacterium tuberculosis H37Rv strain and the α-glucosidase and glycogen phosphorylase enzymes. Few of the compounds have shown interesting in vitro activity with MIC up to 3.12 μg/mL against M. tuberculosis and very good inhibition of α-glucosidase and glycogen phosphorylase enzymes. The most potent non toxic compound 40 exhibited about 58% ex vivo activity at MIC of 3.12 μg/mL. The present study opens a new gate to synthesize antitubercular agents for diabetic TB patients. In silico docking studies indicate that mycobacterial dihydrofolate reductase is the possible target of these compounds. 相似文献
47.
Jernej Jakse Natasa Stajner Zlata Luthar Jean-Marc Jeltsch Branka Javornik 《Molecular breeding : new strategies in plant improvement》2011,28(2):227-239
Data mining of gene sequences available from various projects dealing with the development of expressed sequence tags (ESTs)
can contribute to the discovery of new microsatellite markers. Our aim was to develop new microsatellite markers in hop isolated
from an enriched cDNA library and from coding GenBank sequences and to test their suitability in hop diversity studies and
for construction of a linkage map. In a set of 614 coding GenBank sequences, 72 containing microsatellites were found (11.7%);
the most frequent were trinucleotide repeats (54.0%) followed by dinucleotide repeats (34.5%). Additionally, 11 sequences
containing microsatellites were isolated from an enriched cDNA library. A total of 34 primer pairs were designed, 29 based
on GenBank sequences and five on sequences from the cDNA enriched library. Twenty-seven (79.4%) coding microsatellites were
successfully amplified and used in diversity and linkage mapping studies. Eleven primer pairs amplified 12 coding microsatellite
loci suitable for mapping and were placed on female and male linkage maps. We were able to extend previous simple sequence
repeat (SSR) female, male and integral maps by 38.8, 25.8 and 40.0 cM, respectively. In the diversity study, 36 diverse hop
genotypes were analyzed. Twenty-four coding microsatellites were polymorphic, 17 showing co-dominant behavior and 7 primer
pairs amplifying three or more bands in some hop genotypes. Altogether, 143 microsatellite DNA fragments were amplified and
they revealed a clear separation of hop genotypes according to geographical region, use or breeding history. In addition,
a discussion and comparison of results with other plant coding/EST SSR studies is presented. Our results showed that these
microsatellite markers can enhance hop diversity and linkage mapping studies and are a comparable marker system to non-coding
SSRs. 相似文献
48.
49.
Background
The existence of neural stem and progenitor cells (together termed neural precursor cells) in the adult mammalian brain has sparked great interest in utilizing these cells for regenerative medicine strategies. Endogenous neural precursors within the adult forebrain subependyma can be activated following injury, resulting in their proliferation and migration toward lesion sites where they differentiate into neural cells. The administration of growth factors and immunomodulatory agents following injury augments this activation and has been shown to result in behavioural functional recovery following stroke.Methods and Findings
With the goal of enhancing neural precursor migration to facilitate the repair process we report that externally applied direct current electric fields induce rapid and directed cathodal migration of pure populations of undifferentiated adult subependyma-derived neural precursors. Using time-lapse imaging microscopy in vitro we performed an extensive single-cell kinematic analysis demonstrating that this galvanotactic phenomenon is a feature of undifferentiated precursors, and not differentiated phenotypes. Moreover, we have shown that the migratory response of the neural precursors is a direct effect of the electric field and not due to chemotactic gradients. We also identified that epidermal growth factor receptor (EGFR) signaling plays a role in the galvanotactic response as blocking EGFR significantly attenuates the migratory behaviour.Conclusions
These findings suggest direct current electric fields may be implemented in endogenous repair paradigms to promote migration and tissue repair following neurotrauma. 相似文献50.
The hypothalamus has long been recognized as a major site in the central nervous system (CNS) where a spectrum of internal and external environmental information is integrated for energy homeostasis. The isolation and sequencing of leptin in the mid 90 s, together with the demonstration of leptin administration's ability to correct the obesity syndrome in leptin-deficient ob/ob mice and humans by suppressing food intake and weight gain in laboratory rodents, confirmed the hypothesized existence of a direct humoral signal from adipose tissue to the hypothalamus, thus integrating the energy-related signals. In the 80 s, neuropeptide Y (NPY) was identified as a potent appetite-stimulating neuropeptide produced, released and acting locally within the hypothalamus. This is recognized as a major physiological appetite transducer and central neurochemical substrate receiving, interpreting and processing incoming information on energy status. More recently, ghrelin, produced in the stomach and released into the general circulation, has drawn attention as the other limb of the feedback circuit that stimulates appetite at NPY network level. Prolonged fasting suppresses serum leptin, while suppressing TSH secretion. Intervention with leptin replacement can prevent fasting-induced changes in TSH, suggesting that leptin regulates TSH. Low leptin levels in sportsmen and sportswomen as well as in recreational runners are consistent with reduction in body fat, but are also influenced by the presence of low insulin, hypothyroxemia, and elevated cortisol levels. These metabolic adaptations to chronic energy deficits indicate a role in leptin regulation. A study within the general population found that activity levels and leptin were significantly negatively associated in both sexes. Circulating ghrelin levels, however, do not change during energy expenditure. 相似文献