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91.
Spatial Independent Component Analysis (ICA) decomposes the time by space functional MRI (fMRI) matrix into a set of 1-D basis time courses and their associated 3-D spatial maps that are optimized for mutual independence. When applied to resting state fMRI (rsfMRI), ICA produces several spatial independent components (ICs) that seem to have biological relevance - the so-called resting state networks (RSNs). The ICA problem is well posed when the true data generating process follows a linear mixture of ICs model in terms of the identifiability of the mixing matrix. However, the contrast function used for promoting mutual independence in ICA is dependent on the finite amount of observed data and is potentially non-convex with multiple local minima. Hence, each run of ICA could produce potentially different IC estimates even for the same data. One technique to deal with this run-to-run variability of ICA was proposed by [1] in their algorithm RAICAR which allows for the selection of only those ICs that have a high run-to-run reproducibility. We propose an enhancement to the original RAICAR algorithm that enables us to assign reproducibility p-values to each IC and allows for an objective assessment of both within subject and across subjects reproducibility. We call the resulting algorithm RAICAR-N (N stands for null hypothesis test), and we have applied it to publicly available human rsfMRI data (http://www.nitrc.org). Our reproducibility analyses indicated that many of the published RSNs in rsfMRI literature are highly reproducible. However, we found several other RSNs that are highly reproducible but not frequently listed in the literature. 相似文献
92.
Benito J Shi Y Szymanska B Carol H Boehm I Lu H Konoplev S Fang W Zweidler-McKay PA Campana D Borthakur G Bueso-Ramos C Shpall E Thomas DA Jordan CT Kantarjian H Wilson WR Lock R Andreeff M Konopleva M 《PloS one》2011,6(8):e23108
Recent studies indicate that interactions between leukemia cells and the bone marrow (BM) microenvironment promote leukemia cell survival and confer resistance to anti-leukemic drugs. There is evidence that BM microenvironment contains hypoxic areas that confer survival advantage to hematopoietic cells. In the present study we investigated whether hypoxia in leukemic BM contributes to the protective role of the BM microenvironment. We observed a marked expansion of hypoxic BM areas in immunodeficient mice engrafted with acute lymphoblastic leukemia (ALL) cells. Consistent with this finding, we found that hypoxia promotes chemoresistance in various ALL derived cell lines. These findings suggest to employ hypoxia-activated prodrugs to eliminate leukemia cells within hypoxic niches. Using several xenograft models, we demonstrated that administration of the hypoxia-activated dinitrobenzamide mustard, PR-104 prolonged survival and decreased leukemia burden of immune-deficient mice injected with primary acute lymphoblastic leukemia cells. Together, these findings strongly suggest that targeting hypoxia in leukemic BM is feasible and may significantly improve leukemia therapy. 相似文献
93.
Mtgr1 is a transcriptional corepressor that is required for maintenance of the secretory cell lineage in the small intestine
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94.
95.
Panda G Shagufta Srivastava AK Sinha S 《Bioorganic & medicinal chemistry letters》2005,15(23):5222-5225
A series of 2-hydroxy-aminoalkyl derivatives of diaryloxy methano phenanthrenes were synthesized from nucleophilic opening of oxirane with different amines. These compounds were evaluated for their antitubercular activity against Mycobacterium tuberculosis H(37)R(v) in vitro and showed MIC in the range of 3.12-25microg/ml. 相似文献
96.
97.
Das A Chakraborti P Chatterjee U Monddal G Chatterjee BP 《Indian journal of experimental biology》2005,43(12):1170-1175
Enzymed-linked immunosorbent assay of hilsa and pomfret muscle extracts showed specific IgE binding to ten allergic patients' sera, the results corroborated to that of skin prick test. Comparison of allergen profiles of the two fish extracts by immunoblotting revealed a common antigenic protein of 50 kDa and some high molecular weight fish allergens instead of low molecular weight parvalbumin found in several fishes. Purified and well characterized fish allergens are always considered better than crude fish extracts for diagnostic use. 相似文献
98.
Kobza K Camporeale G Rueckert B Kueh A Griffin JB Sarath G Zempleni J 《The FEBS journal》2005,272(16):4249-4259
Histones are modified post-translationally, e.g. by methylation of lysine and arginine residues, and by phosphorylation of serine residues. These modifications regulate processes such as gene expression, DNA repair, and mitosis and meiosis. Recently, evidence has been provided that histones are also modified by covalent binding of the vitamin biotin. The aims of this study were to identify biotinylation sites in histone H3, and to investigate the crosstalk among histone biotinylation, methylation and phosphorylation. Synthetic peptides based on the sequence of human histone H3 were used as substrates for enzymatic biotinylation by biotinidase; biotin in peptides was probed using streptavidin peroxidase. These studies provided evidence that K4, K9 and K18 in histone H3 are good targets for biotinylation; K14 and K23 are relatively poor targets. Antibodies were generated to histone H3, biotinylated either at K4, K9 or K18. These antibodies localized to nuclei in human placental cells in immunocytochemistry and immunoblotting experiments, suggesting that lysines in histone H3 are biotinylated in vivo. Dimethylation of R2, R8 and R17 increased biotinylation of K4, K9 and K18, respectively, by biotinidase; phosphorylation of S10 abolished biotinylation of K9. These observations are consistent with crosstalk between biotinylation of histones and other known modifications of histones. We speculate that this crosstalk provides a link to known roles for biotin in gene expression and cell proliferation. 相似文献
99.
Gupta S Banerjee M Poddar A Banerjee A Basu G Roy D Bhattacharyya B 《Biochemistry》2005,44(30):10181-10188
Isotypes of vertebrate tubulin have variable amino acid sequences, which are clustered at their C-terminal ends. Isotypes bind colchicine at different on-rates and affinity constants. The kinetics of colchicine binding to purified (unfractionated) brain tubulin have been reported to be biphasic under pseudo-first-order conditions. Experiments with individual isotypes established that the presence of beta(III) in the purified tubulin is responsible for the biphasic kinetics. Because the isotypes mainly differ at the C termini, the colchicine-binding kinetics of unfractionated tubulin and the beta(III) isotype, cleaved at the C termini, have been tested under pseudo-first-order conditions. Removal of the C termini made no difference to the nature of the kinetics. Sequence alignment of different beta isotypes of tubulin showed that besides the C-terminal region, there are differences in the main body as well. To establish whether these differences lie at the colchicine-binding site or not, homology modeling of all beta-tubulin isotypes was done. We found that the isotypes differed from each other in the amino acids located near the A ring of colchicine at the colchicine-binding site on beta tubulin. While the beta(III) isotype has two hydrophilic residues (serine(242) and threonine(317)), both beta(II) and beta(IV) have two hydrophobic residues (leucine(242) and alanine(317)). beta(II) has isoleucine at position 318, while beta(III) and beta(IV) have valine at that position. Thus, these alterations in the nature of the amino acids surrounding the colchicine site could be responsible for the different colchicine-binding kinetics of the different isotypes of tubulin. 相似文献
100.
Miura A Sajan MP Standaert ML Bandyopadhyay G Kahn CR Farese RV 《Biochemistry》2004,43(49):15503-15509
Phosphatidylinositol 3-kinase (PI3K)-dependent activation of atypical protein kinase C (aPKC) is required for insulin-stimulated glucose transport. Although insulin receptor substrate-1 (IRS-1) and IRS-2, among other factors, activate PI3K, there is little information on the relative roles of IRS-1and IRS-2 during aPKC activation by insulin action in specific cell types. Presently, we have used immortalized brown adipocytes in which either IRS-1 or IRS-2 has been knocked out by recombinant methods to examine IRS-1 and IRS-2 requirements for activation of aPKC. We have also used these adipocytes to see if IRS-1 and IRS-2 are required for activation of Cbl, which is required for insulin-stimulated glucose transport and has been found to function upstream of both PI3K/aPKC and Crk during thiazolidinedione action in 3T3/L1 adipocytes [Miura et al. (2003) Biochemistry 42, 14335]. In brown adipocytes in which either IRS-1 or IRS-2 was knocked out, insulin-induced increases in aPKC activity and glucose transport were markedly diminished. These effects of insulin on aPKC and glucose transport were fully restored by retroviral-mediated expression of IRS-1 or IRS-2 in their respective knockout cells. Knockout of IRS-1 or IRS-2 also inhibited insulin-induced increases in Cbl binding to the p85 subunit of PI3K, which, along with IRS-1/2, may be required for activation of PI3K, aPKC, and glucose transport during insulin action in 3T3/L1 adipocytes. These findings provide evidence that directly links both IRS-1 and IRS-2 to aPKC activation in immortalized brown adipocytes, and further suggest that IRS-1 and IRS-2 are required for the activation of Cbl/PI3K during insulin action in these cells. 相似文献