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991.
Tanahashi T Osabe D Nomura K Shinohara S Kato H Ichiishi E Nakamura N Yoshikawa T Takata Y Miyamoto T Shiota H Keshavarz P Yamaguchi Y Kunika K Moritani M Inoue H Itakura M 《Human genetics》2006,120(4):527-542
Several linkage studies have predicted that human chromosome 20q is closely related to type 2 diabetes, but there is no clear evidence that certain variant(s) or gene(s) have strong effects on the disease within this region. To examine disease susceptibility variant in Japanese, verified SNPs from the databases, with a minor allele frequency larger than 0.15, were selected at 10-kb intervals across a 19.31-Mb region (20q11.21-13.13), which contained 291 genes, including hepatocyte nuclear factor 4α (HNF4α). As a result, a total of 1,147 SNPs were genotyped with TaqMan assay using 1,818 Japanese samples. By searching for HNF4α as a representative disease-susceptible gene, no variants of HNF4α were strongly associated with disease. To identify other genetic variant related with disease, we designed an extensive two-stage association study (725 first and 1,093 second test samples). Although SNP1146 (rs220076) was selected as a landmark within the 19.31 Mb region, the magnitude of the nominal P value (P = 0.0023) was rather weak. Subsequently, a haplotype-based association study showed that two common haplotypes were weakly associated with disease. All of these tests resulted in non-significance after adjusting for Bonferroni’s correction and the false discovery rate to control for the impact of multiple testing. Contrary to the initial expectations, we could not conclude that certain SNPs had a major effect on this promising locus within the framework presented here. As a way to extend our observations, we emphasize the importance of a subsequent association study including replication and/or meta-analysis in multiple populations.Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users. 相似文献
992.
993.
Shunkei Enoki Akinori Shimizu Chisato Hayashi Hirotake Imanishi Osamu Hashizume Kazuyuki Mekada Hitoshi Suzuki Tetsuo Hashimoto Kazuto Nakada Jun-Ichi Hayashi 《Experimental Animals》2014,63(1):21-30
Previous reports have shown that transmitochondrial mito-mice with nuclear DNA from
Mus musculus and mtDNA from M. spretus do not express
respiration defects, whereas those with mtDNA from Rattus norvegicus
cannot be generated from ES cybrids with mtDNA from R. norvegicus due to
inducing significant respiration defects and resultant losing multipotency. Here, we
isolated transmitochondrial cybrids with mtDNA from various rodent species classified
between M. spretus and R. norvegicus, and compared the
O2 consumption rates. The results showed a strong negative correlation
between phylogenetic distance and reduction of O2 consumption rates, which
would be due to the coevolution of nuclear and mitochondrial genomes and the resultant
incompatibility between the nuclear genome from M. musculus and the
mitochondrial genome from the other rodent species. These observations suggested that
M. caroli was an appropriate mtDNA donor to generate transmitochondrial
mito-mice with nuclear DNA from M. musculus. Then, we generated ES
cybrids with M. caroli mtDNA, and found that these ES cybrids expressed
respiration defects without losing multipotency and can be used to generate
transmitochondrial mito-mice expressing mitochondrial disorders. 相似文献
994.
Nie Tang Takashi Matsuzaka Marii Suzuki Yuta Nakano Hui Zao Tomotaka Yokoo Noriko Suzuki-Kemuriyama Motoko Kuba Yuka Okajima Yoshinori Takeuchi Kazuto Kobayashi Hitoshi Iwasaki Shigeru Yatoh Akimitsu Takahashi Hiroaki Suzuki Hirohito Sone Masako Shimada Yoshimi Nakagawa Naoya Yahagi Nobuhiro Yamada Hitoshi Shimano 《Biochemical and biophysical research communications》2014
ELOVL family member 6, elongation of very long-chain fatty acids (Elovl6) is a microsomal enzyme that regulates the elongation of C12–16 saturated and monounsaturated fatty acids and is related to the development of obesity-induced insulin resistance via the modification of the fatty acid composition. In this study, we investigated the role of systemic Elovl6 in the pancreatic islet and β-cell function. Elovl6 is expressed in both islets and β-cell lines. In mice fed with chow, islets of the Elovl6−/− mice displayed normal architecture and β-cell mass compared with those of the wild-type mice. However, when fed a high-fat, high-sucrose (HFHS) diet, the islet hypertrophy in response to insulin resistance observed in normal mice was attenuated and glucose-stimulated insulin secretion (GSIS) increased in the islets of Elovl6−/− mice compared with those of the wild-type mice. Enhanced GSIS in the HFHS Elovl6−/− islets was associated with an increased ATP/ADP ratio and the suppression of ATF-3 expression. Our findings suggest that Elovl6 could be involved in insulin secretory capacity per β-cell and diabetes. 相似文献
995.
Ikeda K Nakamura H Arakawa M Toshiyuki Koiwa Matsumoto N 《FEMS microbiology ecology》2005,51(2):293-301
Eighty-three isolates of the violet root rot fungus, Helicobasidium mompa, were collected in a tulip tree plantation and analyzed for the dynamics of double-stranded (ds) RNA for five years. They were divided into eight mycelial compatibility groups (MCGs). Prevalent MCGs 60 and 68 included 61 and 11 isolates, respectively. Electrophoretic profiles of dsRNA in the first year collection of MCG 60 contained no or a single large dsRNA (more than 10 kb) with or without small dsRNAs (ca. 2.0-2.5 kb). Additional dsRNA fragments, i.e., a middle dsRNA (ca. 8.0 kb) or another type of small dsRNAs, became evident within MCG 60 isolates with time. Northern hybridization revealed the relatedness of all large and middle dsRNA fragments within MCG 60 but small fragments of dsRNA were variable. Large dsRNA fragment differed from that in other MCGs even in the same field. Correlation between specific dsRNA fragments and hypovirulence was not observed. Possible explanations for the accumulation of dsRNA fragments during the growth of disease patch by MCG 60 are discussed in terms of their internal changes such as evolution of novel dsRNA fragments from pre-existing viruses or fungal genomic DNA and horizontal transmissions. 相似文献
996.
Kawano A Tsukimoto M Mori D Noguchi T Harada H Takenouchi T Kitani H Kojima S 《Biochemical and biophysical research communications》2012,420(1):102-107
Activation of the P2X7 receptor of macrophages plays an important role in inflammation. We recently reported that co-expression of P2X4 receptor with P2X7 receptor facilitates P2X7 receptor-mediated cell death via Ca(2+) influx. However, it remained unclear whether P2X4 receptor is involved in P2X7 receptor-mediated inflammatory responses, such as cytokine production. Here, we present evidence that P2X4 receptor modulates P2X7 receptor-dependent inflammatory functions. Treatment of mouse macrophage RAW264.7 cells with 1mM ATP induced high mobility group box 1 (HMGB1) release and IL-1β production via activation of P2X7 receptor. Knockdown of P2X4 receptor or removal of extracellular Ca(2+) suppressed ATP-induced release of both HMGB1 and IL-1β. On the other hand, knockdown of P2X4 receptor or removal of extracellular Ca(2+) enhanced P2X7-dependent LC3-II expression (an index of autophagy), suggesting that P2X4 receptor suppresses P2X7-mediated autophagy. Since LC3-II expression was inhibited by pretreatment with antioxidant and NADPH oxidase inhibitor, we examined P2X7-mediated production of reactive oxygen species (ROS). We found that activation of P2X7 receptor-mediated production of ROS was significantly facilitated in P2X4-knockdown cells, suggesting that co-expression of P2X4 receptor with P2X7 receptor may suppress anti-inflammatory function-related autophagy via suppression of ROS production. We conclude that co-expression of P2X4 receptor with P2X7 receptor enhances P2X7-mediated inflammation through both facilitation of release of cytokines and suppression of autophagy. 相似文献
997.
Otomo A Kunita R Suzuki-Utsunomiya K Mizumura H Onoe K Osuga H Hadano S Ikeda JE 《Biochemical and biophysical research communications》2008,370(1):87-92
Loss of function mutations in the ALS2 gene account for a number of juvenile/infantile recessive motor neuron diseases, indicating that its gene product, ALS2/alsin, plays a crucial role in maintenance and survival for a subset of neurons. ALS2 acts as a guanine nucleotide exchange factor (GEF) for the small GTPase Rab5 and is implicated in endosome dynamics in cells. However, the role of ALS2 in neurons remains unclear. To elucidate the neuronal ALS2 functions, we investigate cellular phenotypes of ALS2-deficient primary cultured neurons derived from Als2-knockout (KO) mice. Here, we show that ALS2 deficiency results not only in the delay of axon outgrowth in hippocampal neurons, but also in a decreased level of the fluid phase horseradish peroxidase (HRP) uptake, which represents the activity for macropinocytic endocytosis, in cortical neurons. Thus, ALS2 may act as a modulator in neuronal differentiation and/or development through regulation of membrane dynamics. 相似文献
998.
999.
α-Galactosidase gene mutations in Fabry disease: heterogeneous expressions of mutant enzyme proteins
Toshika Okumiya Satoshi Ishii Ryoichi Kase Sachiko Kamei Hitoshi Sakuraba Yoshiyuki Suzuki 《Human genetics》1995,95(5):557-561
Five point mutations were identified in unrelated Japanese Fabry disease hemizygotes: three new missense mutations, C142Y (425 G A), A156V (467 C T), and L166V (496 C G) in exon 3; one new splice site mutation at the 3 end of the consensus sequence in exon 4; one previously reported nonsense mutation, W44X (131 G A). C142Y expressed 50% of the normal enzyme protein in COS-1 cells, but catalytic activity was not detected. Both A156V and L166V expressed significant amounts of residual enzyme activity (6.7% and 9.8%) and enzyme proteins (10% each), the latter were more thermolabile at neutral pH than at acid pH, in vitro. 相似文献
1000.
Makoto Moro Ryuzo Torii Hitoshi Koizumi Yoichi Inada Yasuo Etoh Hiroshi Miyata Yoshikuni Tanioka 《Primates; journal of primatology》1995,36(2):249-257
A homologous double-antibody radioimmunoassay developed for humans was used to measure serum prolactin, progesterone, and
estradiol in common marmosets. In the ovarian cycle of common marmosets, serum progesterone began to increase after an estradiol
surge, attained a peak level, and then declined before the ensuing pre-ovulatory rise in estradiol. During the luteal phase,
the change in serum concentrations of estradiol was synchronized with that of progesterone. During the ovarian cycle there
was no consistent change in serum prolactin concentrations. During the last 75 days of pregnancy the prolactin level was higher
than during the ovarian cycle and the first 70 days of pregnancy. Moreover, during lactation, mothers with suckling twin infants
had a higher prolactin level than during the final stage of pregnancy. 相似文献