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81.
Sato A Endo H Umetsu K Sone H Yanagisawa Y Saigusa A Aita S Kagawa Y 《Bioscience reports》2003,23(5-6):313-337
Mitochondrial DNA (mtDNA) is highly susceptible to mutations that result in polymorphisms and diseases including diabetes. We analyzed heteroplasmy, polymorphisms related to diabetes, and complementation by fusogenic proteins. Cytoplast fusion and microinjection allow, defects in mutated mtDNA inside a heteroplasmic cell to be complemented by fusing two mitochondria via human fusogenic proteins. We characterized three hfzos as well as two OPAls that prevent apoptosis. Two coiled coil domains and GTPase domains in these fusogenic proteins regulate membrane fusion. The hfzo genes were expressed mainly in the brain and in muscle that are postmitotic, but not in the pancreas. Under the influence of polymorphisms of mtDNA and nDNA, the vicious circle of reactive oxygen species and mutations in cell can be alleviated by mitochondrial fusion. 相似文献
82.
Dietary Zn deficiency does not influence systemic blood pressure and vascular nitric oxide signaling in normotensive rats 总被引:1,自引:1,他引:0
Sato M Kurihara N Moridaira K Sakamoto H Tamura J Wada O Yanagisawa H 《Biological trace element research》2003,91(2):157-171
Because zinc (Zn) is an important component for cell protection against certain oxygen species, it has been suggested that
Zn deficiency impairs the potent oxidant defense capacity, which is constitutively provided in the vascular system. However,
the influence of dietary Zn deficiency on systemic blood pressure and vascular system is controversial and unclear. We therefore
examine the effect of dietary Zn deficiency on systemic blood pressure, a potent superoxide scavenger, aortic Cu/Zn superoxide
dismutase (SOD) activity, a most representative synthase of the endothelium-derived relaxing factor, and aortic endothelial
nitric oxide synthase (eNOS) expression. Furthermore, the direct effects of intravenous administration of NOS inhibitor, N
ω-nitro-l-arginine methyl ester (l-NAME), and a SOD mimetic compound, tempol, in normotensives were tested in Wistar-Kyoto (WKY) rats. A Zn-deficient diet (4
wk) contributed to growth retardation, the decrease in thymus weight, and the lower levels of serum Zn compared with the standard
diet group. However, no significant difference in conscious systolic and diastolic blood pressure was found in the Zn-deficiency
group. The administration of l-NAME caused an increase in the mean arterial pressure (MAP) levels in the two groups of rats and the involvement of the vasodilator
nitric oxide (NO) in the regulation of systemic BP in the normotensive state. On the other hand, administration of the superoxide
scavenger, tempol, led to a decrease in MAP levels in the two groups of rats, indicating the participation of the oxygen free
radical, superoxide, in the maintenance of the systemic BP in a normotensive state. There were no significant differences
between the Zn-deficient diet group and the standard diet group in the normotensive state. eNOS expression and Cu/Zn SOD activity
in the aorta were also intact in Zn-deficient normotensive rats. These findings suggest that the 4 wk of Zn deficiency was
inadequate to alter systemic blood pressure and focal NO signaling in the normotensive state. Long-term Zn deficiency affects
the neuronal, immune, and hematopoietic systems, which contribute to systemic and/or local circulation. However, Zn deficiency
alone does not cause hypertension and local vascular dysfunction in the normotensive state. 相似文献
83.
Watanabe M Yanagisawa J Kitagawa H Takeyama K Ogawa S Arao Y Suzawa M Kobayashi Y Yano T Yoshikawa H Masuhiro Y Kato S 《The EMBO journal》2001,20(6):1341-1352
One class of the nuclear receptor AF-2 coactivator complexes contains the SRC-1/TIF2 family, CBP/p300 and an RNA coactivator, SRA. We identified a subfamily of RNA-binding DEAD-box proteins (p72/p68) as a human estrogen receptor alpha (hER alpha) coactivator in the complex containing these factors. p72/p68 interacted with both the AD2 of any SRC-1/TIF2 family protein and the hER alpha A/B domain, but not with any other nuclear receptor tested. p72/p68, TIF2 (SRC-1) and SRA were co-immunoprecipitated with estrogen-bound hER alpha in MCF7 cells and in partially purified complexes associated with hER alpha from HeLa nuclear extracts. Estrogen induced co-localization of p72 with hER alpha and TIF2 in the nucleus. The presence of p72/p68 potentiated the estrogen-induced expression of the endogenous pS2 gene in MCF7 cells. In a transient expression assay, a combination of p72/p68 with SRA and one TIF2 brought an ultimate synergism to the estrogen-induced transactivation of hER alpha. These findings indicate that p72/p68 acts as an ER subtype-selective coactivator through ER alpha AF-1 by associating with the coactivator complex to bind its AF-2 through direct binding with SRA and the SRC-1/TIF2 family proteins. 相似文献
84.
Takebayashi-Suzuki K Yanagisawa M Gourdie RG Kanzawa N Mikawa T 《Development (Cambridge, England)》2000,127(16):3523-3532
The rhythmic heart beat is coordinated by electrical impulses transmitted from Purkinje fibers of the cardiac conduction system. During embryogenesis, the impulse-conducting cells differentiate from cardiac myocytes in direct association with the developing endocardium and coronary arteries, but not with the venous system. This conversion of myocytes into Purkinje fibers requires a paracrine interaction with blood vessels in vivo, and can be induced in vitro by exposing embryonic myocytes to endothelin-1 (ET-1), an endothelial cell-associated paracrine factor. These results suggest that an endothelial cell-derived signal is capable of inducing juxtaposed myocytes to differentiate into Purkinje fibers. It remains unexplained how Purkinje fiber recruitment is restricted to subendocardial and periarterial sites but not those juxtaposed to veins. Here we show that while the ET-receptor is expressed throughout the embryonic myocardium, introduction of the ET-1 precursor (preproET-1) in the embryonic myocardium is not sufficient to induce myocytes to differentiate into conducting cells. ET converting enzyme-1 (ECE-1), however, is expressed preferentially in endothelial cells of the endocardium and coronary arteries where Purkinje fiber recruitment takes place. Retroviral-mediated coexpression of both preproET-1 and ECE-1 in the embryonic myocardium induces myocytes to express Purkinje fiber markers ectopically and precociously. These results suggest that expression of ECE-1 plays a key role in defining an active site of ET signaling in the heart, thereby determining the timing and location of Purkinje fiber differentiation within the embryonic myocardium. 相似文献
85.
S. Ogawa R. Yoshino K. Angata M. Iwamoto M. Pi K. Kuroe K. Matsuo T. Morio H. Urushihara K. Yanagisawa Y. Tanaka 《Molecular genetics and genomics : MGG》2000,263(3):514-519
We present an overview of the gene content and organization of the mitochondrial genome of Dictyostelium discoideum. The mitochondria genome consists of 55,564?bp with an A + T content of 72.6%. The identified genes include those for two ribosomal RNAs (rnl and rns), 18 tRNAs, ten subunits of the NADH dehydrogenase complex (nad1, 2, 3, 4, 4L, 5, 6, 7, 9 and 11), apocytochrome b (cytb), three subunits of the cytochrome oxidase (cox1/2 and 3), four subunits of the ATP synthase complex (atp1, 6, 8 and 9), 15 ribosomal proteins, and five other ORFs, excluding intronic ORFs. Notable features of D. discoideum mtDNA include the following. (1) All genes are encoded on the same strand of the DNA and a universal genetic code is used. (2) The cox1 gene has no termination codon and is fused to the downstream cox2 gene. The 13 genes for ribosomal proteins and four ORF genes form a cluster 15.4?kb long with several gene overlaps. (3) The number of tRNAs encoded in the genome is not sufficient to support the synthesis of mitochondrial protein. (4) In total, five group I introns reside in rnl and cox1/2, and three of those in cox1/2 contain four free-standing ORFs. We compare the genome to other sequenced mitochondrial genomes, particularly that of Acanthamoeba castellanii. 相似文献
86.
87.
88.
Abe Y Sakurai T Yamada T Nakamura T Yanagisawa M Goto K 《Biochemical and biophysical research communications》2000,275(2):524-531
Several missense mutations of the endothelin-B receptor (EDNRB) associated with Hirschsprung disease have recently been identified. Five mutated EDNRB (A183G, W276C, R319W, M374I and P383L) cDNAs were transiently expressed in several cell lines to examine the effects of these mutations. Ligand-receptor binding experiments demonstrated that all mutants examined here accept endothelins with a high affinity. Especially, the affinity of endothelins to P383L was increased. However, the number of binding sites of A183G, W276C and P383L was markedly decreased. The subcellular localization of these mutant receptors was the same as that of wild-type EDNRB, whereas the amount of protein of each mutant receptor was decreased. All mutant receptors were impaired in intracellular Ca(2+) mobilization. These findings indicate that these missense mutations result in loss of function of EDNRB, and may provide the molecular pathological basis of Hirschsprung disease in some individuals. 相似文献
89.
In the shallow waters of Lake Tanganyika, a benthic cichlid Xenotilapia boulengeri rests in a cluster around the nesting sites of substrate-brooding cichlids Lepidiolamprologus attenuatus and L. elongatus . Experimental removal of parent Lepidiolamprologus guarding free-swimming young drastically reduced the number of X. boulengeri around these nesting sites within a few days, suggesting that their presence has a positive effect on attracting X. boulengeri . Xenotilapia boulengeri were less frequently disturbed by the scale-eating cichlids Perissodus microlepis and Plecodus straeleni when they remained near nesting sites of these species than when stayed away. This was attributed to the territorial behaviour of guarding parents who drove away scale-eaters at greater distances, while allowing X. boulengeri , harmless to their young, to approach the nesting site. It is concluded that a clumped distribution of X. boulengeri results from differential tolerance of breeding parents toward intruders that produces a safety zone from scale-eaters. 相似文献
90.
Shinji Sudoh Yuuki Kawamura Shinji Sato §Rong Wang ‡Takaomi C. Saido †Fumitaka Oyama Yoshiyuki Sakaki Hiroto Komano Katsuhiko Yanagisawa 《Journal of neurochemistry》1998,71(4):1535-1543
Abstract: Mutations in the presenilin genes PS1 and PS2 cause the most common form of early-onset familial Alzheimer's disease. The influence of PS1 mutations on the generation of endogenous intracellular amyloid β-protein (Aβ) species was assessed using a highly sensitive immunoblotting technique with inducible mouse neuro-blastoma (Neuro 2a) cell lines expressing the human wild-type (wt) or mutated PS1 (M146L or Δexon 10). The induction of mutated PS1 increased the intracellular levels of two distinct Aβ species ending at residue 42 that were likely to be Aβ1–42 and its N-terminally truncated variant(s) Aβx-42. The induction of mutated PS1 resulted in a higher level of intracellular Aβ1–42 than of intracellular Aβx-42, whereas extracellular levels of Aβ1–42 and Aβx-42 were increased proportionally. In addition, the intracellular generation of these Aβ42 species in wt and mutated PS1 -induced cells was completely blocked by brefeldin A, whereas it exhibited differential sensitivities to monensin: the increased accumulation of intracellular Aβx-42 versus inhibition of intracellular Aβ1–42 generation. These data strongly suggest that Aβx-42 is generated in a proximal Golgi, whereas Aβ1–42 is generated in a distal Golgi and/or a post-Golgi compartment. Thus, it appears that PS1 mutations enhance the degree of 42-specific γ-secretase cleavage that occurs in the normal β-amyloid precursor protein processing pathway (a) in the endoplasmic reticulum or the early Golgi apparatus prior to β-secretase cleavage or (b) in the distinct sites where Aβx-42 and Aβ1–42 are generated. 相似文献