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151.
Diana Ronai Dunshee Travis W. Bainbridge Noelyn M. Kljavin Jose Zavala-Solorio Amy C. Schroeder Ruby Chan Racquel Corpuz Manda Wong Wei Zhou Gauri Deshmukh Justin Ly Daniel P. Sutherlin James A. Ernst Junichiro Sonoda 《The Journal of biological chemistry》2016,291(11):5986-5996
FGF21 is a stress-induced hormone with potent anti-obesity, insulin-sensitizing, and hepatoprotective properties. Although proteolytic cleavage of recombinant human FGF21 in preclinical species has been observed previously, the regulation of endogenously produced FGF21 is not well understood. Here we identify fibroblast activation protein (FAP) as the enzyme that cleaves and inactivates human FGF21. A selective chemical inhibitor, immunodepletion, or genetic deletion of Fap stabilized recombinant human FGF21 in serum. In addition, administration of a selective FAP inhibitor acutely increased circulating intact FGF21 levels in cynomolgus monkeys. On the basis of our findings, we propose selective FAP inhibition as a potential therapeutic approach to increase endogenous FGF21 activity for the treatment of obesity, type 2 diabetes, non-alcoholic steatohepatitis, and related metabolic disorders. 相似文献
152.
Thy28 protein is conserved among plants, bacteria, and mammalian cells. Nuclear Thy28 protein is substantially expressed in
testis, liver, and immune cells such as lymphocytes. Lymphocyte apoptosis plays a crucial role in homeostasis and formation
of a diverse lymphocyte repertoire. In this study, we examined whether Thy28 affects induction of apoptosis in WEHI-231 B
lymphoma cells following engagement of membrane immunoglobulin (mIg). Once they were established, the Thy28-overexpressing
WEHI-231 cells showed similar expression levels of IgM and class I major histocompatibility complex (MHC) molecule compared
with controls. The Thy28-overexpressing cells were considerably resistant to loss of mitochondrial membrane potential (ΔΨm),
caspase-3 activation, and increase in annexin-positive cells upon mIg engagement. These changes were concomitant with an increase
in G1 phase associated with upregulation of p27Kip1. The anti-IgM-induced sustained activation of c-Jun N-terminal kinase (JNK), which was associated with late-phase hydrogen
peroxide (H2O2) production, was partially reduced in the Thy28-expressing cells relative to controls. Taken together, the data suggest that
in WEHI-231 B lymphoma cells, Thy28 regulates mIg-mediated apoptotic events through the JNK-H2O2 activation pathway, concomitant with an accumulation of cells in G1 phase associated with upregulation of p27Kip1 in WEHI-231 B lymphoma cells. 相似文献
153.
Thomas Hennig Philipp Maass Junichiro Hayano Stefan Heinrichs 《Journal of biological physics》2006,32(5):383-392
The statistical properties of heart beat intervals of 130 long-term surface electrocardiogram recordings during atrial fibrillation
(AF) are investigated. We find that the distribution of interbeat intervals exhibits a characteristic exponential tail, which
is absent during sinus rhythm, as tested in a corresponding control study with 72 healthy persons. The rate γ of the exponential decay lies in the range 3–12 Hz and shows diurnal variations. It equals, up to statistical uncertainties,
the level of the previously uncovered white noise part of the power spectrum, which is also characteristic for AF. The overall
statistical features can be described by decomposing the intervals into two statistically independent times, where the first
one is associated with a correlated process with 1/f noise characteristics, while the second one belongs to an uncorrelated process and is responsible for the exponential tail.
It is suggested to use γ as a further parameter for a better classification of AF and for the medical diagnosis. The relevance of the findings with
respect to a general understanding of AF is discussed. 相似文献
154.
Taneichi M Tanaka Y Kasai M Mori M Nishida M Yamamura H Mizuguchi J Uchida T 《Bioconjugate chemistry》2006,17(4):899-904
The T-cell receptors of CD4(+) T lymphocytes recognize immunogenic peptide sequences bound within the groove of MHC class II molecules, and the peptides that bind to these molecules are known to share common structural motifs. For example, OVA(323-339), an I-A(d)-binding peptide, involves a motif of the I-A(d) peptide-binding groove. In the present study, OVA peptides of up to 26-mer were sequentially synthesized and screened, and two additional I-A(d) binding OVA peptides, OVA(20-43) and OVA(264-286), were found to stimulate CD4(+) T cells of OVA-immune BALB/c mice. OVA(20-43) involved structural motifs of the I-A(d) peptide-binding groove, while OVA(264-286) did not. The ability of these three I-A(d) binding OVA peptides to induce antigen-specific cytokine production was compared among CD4(+) T cells of mice immunized either with alum-adsorbed OVA (OVA-alum) or OVA chemically coupled to the surface of liposome (OVA-liposome). CD4(+) T cells of mice immunized with OVA-alum produced more cytokines when stimulated with OVA(264-286) than with OVA(323-339), while CD4(+) T cells of mice immunized with OVA-liposome conjugates produced more cytokines when stimulated with OVA(323-339) than with OVA(264-286). OVA(20-43) induced production of comparable levels of cytokines in mice immunized either with OVA-alum or OVA-liposome. Confocal laser scanning microscopic analysis demonstrated that chemically coupled OVA and liposomes were colocalized in APCs until OVA received processing. Three-dimensional structural analysis demonstrated that both OVA(264-286) and OVA(323-339) were present on the surface of OVA, but OVA(20-43) was not. These results suggested that the chemical coupling of OVA to liposome affected antigen processing in APCs and thus resulted in the induction of differential T-cell epitopes as compared with those induced by plain OVA. 相似文献
155.
Deficiency of the tensin2 gene in the ICGN mouse: an animal model for congenital nephrotic syndrome 总被引:1,自引:1,他引:0
A-Ri Cho Kozue Uchio-Yamada Takeshi Torigai Tomomi Miyamoto Ichiro Miyoshi Junichiro Matsuda Tsutomu Kurosawa Yasuhiro Kon Atsushi Asano Nobuya Sasaki Takashi Agui 《Mammalian genome》2006,17(5):407-416
The ICGN mouse is a model for nephrotic syndrome (NS) which presents with proteinuria, hyperlipidemia, and edema. In this
study we attempted to identify the gene(s) responsible for NS. By analyzing albuminuria in 160 (ICGN × MSM)F1 × ICGN backcross progenies, we found that NS in the ICGN mouse is caused by more than one gene. We then performed a quantitative
trait locus (QTL) analysis and detected a QTL with a very high LOD score peak in the telomeric region of Chr 15. By analyzing
the nucleotide sequence of 22 genes located close to the QTL, we found that the tensin2 gene of the ICGN mouse possessed an 8-nucleotide deletion mutation in exon 18, leading to a frameshift and giving rise to
a terminal codon at a premature position. Analyses of in situ hybridization and immunohistochemistry revealed that tensin2 was expressed in podocytes and tubular epithelial cells in normal
mice but not in the ICGN mouse. These data raise the possibility that a mutation of the tensin2 gene is responsible for NS of the ICGN mouse and tensin2 is a prerequisite for the normal kidney function. 相似文献
156.
The developmental expressions of the mRNA of JH synthetic enzymes have been studied using homogenates of the corpora cardiaca-corpora allata (CC-CA) complexes in Bombyx mori [Kinjoh, T., Kaneko, Y., Itoyama, K., Mita, K., Hiruma, K., Shinoda, T., 2007. Control of juvenile hormone biosynthesis in Bombyx mori: cloning of the enzymes in the mevalonate pathway and assessment of their developmental expression in the corpora allata. Insect Biochemistry and Molecular Biology 37, 808-818]. The in situ hybridization analyses in the CC-CA complex showed that the distribution of the mRNAs of all the mevalonate enzymes and juvenile hormone (JH) acid O-methyltransferase occurred only in the CA cells, indicating that the fluctuations of the enzyme mRNA amounts in the CC-CA complexes were derived solely from the CA. In addition, the size of the CA and their nuclei was not associated with the JH synthetic activity by the CA until the pharate adult. Only female adult CA synthesized JH in B. mori, and the CA and the nuclei were significantly larger than those of male CA which do not synthesize JH. 相似文献
157.
158.
The effects of JHA (ZR-515) application or brain implantation on metamorphosis and adult development were examined in the last instar larvae and pupae of Mamestra brassicae. When JHA was applied to neck-ligated 4- or 5-day-old larvae or to the isolated abdomens of 5-day-old larvae containing implanted prothoracic glands taken from 5-day-old larvae, the insects pupated. Dauer pupae and diapausing pupae treated with JHA showed adult development. By contrast, pupation could not be induced by the application of JHA to 2- or 3-day-old neck-ligated larvae or to the isolated abdomens of 5-day-old larvae containing implanted prothoracic glands from 0-day-old larvae. Implantation of a brain into neck-ligated 3- or 5-day-old larvae (at the beginning of gut emptying and wandering) caused pupation of the host. A similar result was obtained when both a brain and the prothoracic glands from 0- or 5-day-old larvae were implanted into the isolated abdomens of 5-day-old larvae. These results indicate that activation of the prothoracic glands by application of JHA is temporally restricted to the last part of the last larval instar and to the pupal stage, while the activation by prothoracicotropic hormone (PTTH) can occur throughout the last larval instar and the pupal stage. In addition, the implantation of brains or application of JHA to neck-ligated 5-day-old larvae 25 days after ligation seldom induced pupation of the hosts, a result which suggests that larval prothoracic glands maintained under juvenile hormone (JH) or PTTH-free conditions for long periods of time may become insensitive to reactivation by both hormones. 相似文献
159.
160.