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71.
We screened clones for thioredoxin reductase genes with a degenerate PCR-based strategy and have isolated two novel cDNA clones from a mouse thymocyte cDNA library. These encode two distinct thioredoxin reductases (TrxR1 and TrxR2) with 499 and 527 amino acid (aa) residues and calculated molecular masses of 54.5 kDa and 56.8 kDa respectively. These proteins share 90% and 50% aa sequence identity with those of previously cloned human TrxR, containing the redox-active cysteines, FAD binding domain, and the selenocysteine (SeCys) insertion sequence, which is composed of a putative stem-loop sequence located in the 3'-untranslated region (UTR). TrxR2 showing less homology to human TrxR has a mitochondrial translocation signal and a mitochondrial prepeptide protease cleavage site in the N-terminal domain. Transient expression experiments of each gene as fusion proteins with Xpress-tagged protein in NIH 3T3 cells indicated that TrxR1 was localized in the nucleus and cytoplasm and TrxR2 in the mitochondria. Furthermore, we mapped the TrxR1 gene to chromosome 10 (placed 1.71 cR from D10Mit42, lod>3.0) and the TrxR2 gene to chromosome 16 (placed 22.56 cR from D16Mit34, lod>3.0). Thus, the mouse has at least two distinct nuclear genes for TrxR that have different translocation sites in the cell. 相似文献
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Artificial sequences of the 153 amino acids have been designed to fit the main-chain framework of the sperm whale myoglobin (Mb) structure based on a knowledge-based 3D-1D compatibility method. The previously designed artificial globin (DG1) folded into a monomeric, compact, highly helical and globular form with overall dimensions similar to those of the target structure, but it lacked structural uniqueness at the side-chain level [Isogai, Y., Ota, M., Fujisawa, T. , Izuno, H., Mukai, M., Nakamura, H., Iizuka, T., and Nishikawa, K. (1999) Biochemistry 38, 7431-7443]. In this study, we redesigned hydrophobic sites of DG1 to improve the structural specificity. Several Leu and Met residues in DG1 were replaced with beta-branched amino acids, Ile and Val, referring to the 3D profile of DG1 to produce three redesigned globins, DG2-4. These residue replacements resulted in no significant changes of their compactness and alpha-helical contents in the absence of denaturant, whereas they significantly affected the dependence of the secondary structure on the concentration of guanidine hydrochloride. The analyses of the denaturation curves revealed higher global stabilities of the designed globins than that of natural apoMb. Among DG1-4, DG3, in which 11 Leu residues of DG1 are replaced with seven Ile and four Val residues, and one Met residue is replaced with Val, displayed the lowest stability but the most cooperative folding-unfolding transition and the most dispersed NMR spectrum with the smallest line width. The present results indicate that the replacements of Leu (Met) with the beta-branched amino acids at appropriate sites reduce the freedom of side-chain conformation and improve the structural specificity at the expense of stability. 相似文献
74.
Takaya Oguchi Masao Ota Tetsuya Ito Hideaki Hamano Norikazu Arakura Yoshihiko Katsuyama Akira Meguro Shigeyuki Kawa 《PloS one》2015,10(5)
Autoimmune pancreatitis (AIP) is a unique form of chronic pancreatitis characterized by high serum IgG4 concentration and a variety of complicating extra-pancreatic lesions. In particular, lachrymal/salivary gland lesions tend to manifest in a highly active AIP disease state, and several genes are speculated to be associated with the onset of this complication. We therefore searched for candidate susceptibility genes related to lachrymal/salivary gland lesions in a genome-wide association study (GWAS) with the GeneChip Human Mapping 500k Array Set (Affymetrix, CA) that was followed by fine mapping of additional single nucleotide polymorphisms (SNPs) in strongly significant genes with TaqMan assays. Venous blood samples were obtained from 50 type 1 AIP patients with lachrymal/salivary gland lesions (A group) and 53 type 1 AIP patients without (B group). The mean values of IgG and IG4 were both significantly different (P<0.05) between the groups. SNPs that showed a significant association with the A group at the genome-wide level (P<0.0001) were identified and subsequently used in fine SNP mapping of candidate genes. In total, five SNPs had a positive association with complicated AIP (most notably rs2284932 [P=0.0000021]) and five SNPs possessed a negative association (particularly rs9371942 [P=0.00000039]). Among them, KLF7, FRMD4B, LOC101928923, and MPPED2 were further examined for complication susceptibility using additional SNPs that were not included in the GWAS. Individual genotyping of KLF7 rs2284932 revealed that the frequency of the minor C allele was significantly increased (P=0.00062, Pc=0.0018, OR=2.98, 95%CI=1.58-5.65) in group A. The minor T allele of rs4473559 in FRMD4 demonstrated a significant association in the A group (P=0.00015, OR=3.38, 95%CI=1.77-7.65). In the LOC101928923 gene, the frequency of the minor C allele of rs4379306 was significantly decreased in group A in both TaqMan and GWAS analyses. Lastly, the minor C allele of MPPED2 rs514644 carried a significantly increased risk of complications. These four genes may be linked with the onset of lachrymal/salivary gland lesions in type 1 AIP patients and require further study. 相似文献
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76.
Kate?ina Ku?elová Barbora Brodská Ota Fuchs Marie Dobrovolná Petr Soukup Petr Cetkovsky 《PloS one》2015,10(5)
Nucleophosmin 1 (NPM1) mutations are frequently found in patients with acute myeloid leukemia (AML) and the newly generated sequences were suggested to induce immune response contributing to the relatively favorable outcome of patients in this AML subset. We hypothesized that if an efficient immune response against mutated nucleophosmin can be induced in vivo, the individuals expressing HLA alleles suitable for presenting NPM-derived peptides should be less prone to developing AML associated with NPM1 mutation. We thus compared HLA class I frequencies in a cohort of patients with mutated NPM1 (63 patients, NPMc+), a cohort of patients with wild-type NPM1 (94 patients, NPMwt) and in normal individuals (large datasets available from Allele Frequency Net Database). Several HLA allelic groups were found to be depleted in NPMc+ patients, but not in NPMwt compared to the normal distribution. The decrease was statistically significant for HLA B*07, B*18, and B*40. Furthermore, statistically significant advantage in the overall survival was found for patients with mutated NPM1 expressing at least one of the depleted allelic groups. The majority of the depleted alleles were predicted to bind potent NPM-derived immunopeptides and, importantly, these peptides were often located in the unmutated part of the protein. Our analysis suggests that individuals expressing specific HLA allelic groups are disposed to develop an efficient anti-AML immune response thanks to aberrant cytoplasmic localization of the mutated NPM protein. 相似文献
77.
We had previously exploited a method for targeted DNA methylation in budding yeast to succeed in one-hybrid detection of methylation-dependent DNA–protein interactions. Based on this finding, we developed a yeast one-hybrid system to screen cDNA libraries for clones encoding methylated DNA-binding proteins. Concurrent use of two independent bait sequences in the same cell, or dual-bait system, effectively reduced false positive clones, which were derived from methylation-insensitive sequence-specific DNA-binding proteins. We applied the dual-bait system to screen cDNA libraries and demonstrated efficient isolation of clones for methylated DNA-binding proteins. This system would serve as a unique research tool for epigenetics. 相似文献
78.
Atsushi Tominaga Hidetoshi Ota Masafumi Matsui 《Molecular phylogenetics and evolution》2010,54(3):910-921
We investigated the phylogenetic relationships and phylogeography among individuals of the endemic newt (Cynops ensicauda) of the Central Ryukyus, Japan based on the mitochondrial cytochrome b gene. The results of phylogenetic analyses showed the presence of remarkable differentiation between assemblages from the Amami and Okinawa Island Groups, supporting the validity of the subspecies C. e. popei described from the latter on morphological grounds. The group of individuals from Okinawa Island Group was further divided into two distinct subgroups unlike the results of previous morphological and allozyme studies. Geographic ranges of these subgroups overlapped in the northern part of Okinawajima Island. The phylogeographic pattern within the Okinawa Island Group suggests an initial division into two geographically isolated population lineages and subsequent secondary sympatry before formation of reproductive isolation. It is also likely that within the Okinawa Island Group emigration occurred from the central and northern parts of Okinawajima Island to its southern part, as well as to several small islets off its western coast. Within the Amami Island Group, recurring restricted gene flow with isolation by distance seems to have occurred around the southwestern region including three islets southwest of Amamioshima Island. 相似文献
79.
Suzuki A Kobayashi M Matsuda K Matsumoto T Kawakubo M Kumazawa S Koide N Miyagawa S Ota H 《Helicobacter》2010,15(6):538-548
80.