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91.
Masatoshi Murayama Hirohito Hirata Makoto Shiraki Juan L. Iovanna Takayoshi Yamaza Toshio Kukita Toshihisa Komori Takeshi Moriishi Masaya Ueno Tadatsugu Morimoto Masaaki Mawatari Akiko Kukita 《Journal of cellular physiology》2023,238(3):566-581
Nuclear protein 1 (NUPR1) is a stress-induced protein activated by various stresses, such as inflammation and oxidative stress. We previously reported that Nupr1 deficiency increased bone volume by enhancing bone formation in 11-week-old mice. Analysis of differentially expressed genes between wild-type (WT) and Nupr1-knockout (Nupr1-KO) osteocytes revealed that high temperature requirement A 1 (HTRA1), a serine protease implicated in osteogenesis and transforming growth factor-β signaling was markedly downregulated in Nupr1-KO osteocytes. Nupr1 deficiency also markedly reduced HtrA1 expression, but enhanced SMAD1 signaling in in vitro-cultured primary osteoblasts. In contrast, Nupr1 overexpression enhanced HtrA1 expression in osteoblasts, suggesting that Nupr1 regulates HtrA1 expression, thereby suppressing osteoblastogenesis. Since HtrA1 is also involved in cellular senescence and age-related diseases, we analyzed aging-related bone loss in Nupr1-KO mice. Significant spine trabecular bone loss was noted in WT male and female mice during 6−19 months of age, whereas aging-related trabecular bone loss was attenuated, especially in Nupr1-KO male mice. Moreover, cellular senescence-related markers were upregulated in the osteocytes of 6−19-month-old WT male mice but markedly downregulated in the osteocytes of 19-month-old Nupr1-KO male mice. Oxidative stress-induced cellular senescence stimulated Nupr1 and HtrA1 expression in in vitro-cultured primary osteoblasts, and Nupr1 overexpression enhanced p16ink4a expression in osteoblasts. Finally, NUPR1 expression in osteocytes isolated from the bones of patients with osteoarthritis was correlated with age. Collectively, these results indicate that Nupr1 regulates HtrA1-mediated osteoblast differentiation and senescence. Our findings unveil a novel Nupr1/HtrA1 axis, which may play pivotal roles in bone formation and age-related bone loss. 相似文献
92.
Shuhei Takatsuka Takeshi Kubota Yuta Kurashina Sho Kurihara Motoki Hirabayashi Masato Fujioka Hirotaka James Okano Hiroaki Onoe 《Biotechnology and bioengineering》2023,120(8):2371-2377
Adeno-associated virus (AAV)-based gene therapy holds promise as a fundamental treatment for genetic disorders. For clinical applications, it is necessary to control AAV release timing to avoid an immune response to AAV. Here we propose an ultrasound (US)-triggered on-demand AAV release system using alginate hydrogel microbeads (AHMs) with a release enhancer. By using a centrifuge-based microdroplet shooting device, the AHMs encapsulating AAV with tungsten microparticles (W-MPs) are fabricated. Since W-MPs work as release enhancers, the AHMs have high sensitivity to the US with localized variation in acoustic impedance for improving the release of AAV. Furthermore, AHMs were coated with poly-l -lysine (PLL) to adjust the release of AAV. By applying US to the AAV encapsulating AHMs with W-MPs, the AAV was released on demand, and gene transfection to cells by AAV was confirmed without loss of AAV activity. This proposed US-triggered AAV release system expands methodological possibilities in gene therapy. 相似文献
93.
The proteins KdpD and KdpE are crucial to the osmotic regulation of the kdpABC operon that is responsible for the high-affinity K+ ion transport system in Escherichia coli. We demonstrated previously that the response regulator, KdpE, is capable of undergoing Phosphorylation mediated by the sensory protein kinase, KdpD. In this study, we obtained biochemical evidence supporting the view that when KdpE is phosphorylated, it takes on an active form that exhibits relatively high affinity for the kdpABC promoter, which in turn results in activation of the kdpABC operon. It was also suggested that the central hydrophobic domain of KdpD, which is conceivably responsible for membrane anchoring of this protein, plays a role in the signalling mechanism underlying KdpE Phosphorylation in response to hyperosmotic stress. 相似文献
94.
Ota Yoko; Ario Takeshi; Hayashi Koji; Nakagawa Tsuyoshi; Hattori Tsukaho; Maeshima Masayoshi; Asahi Tadashi 《Plant & cell physiology》1992,33(3):225-232
Catalases purified from endosperm glyoxysomes and non-specializedmicrobodies from hypocotyls of castor bean seedlings differedin their specific activity [90164 and 0.894.9kunits (mg protein)1, respectively] and in their constituentsubunits [two subunits of 54 and 56 kDa for the endosperm enzymeand only one of 56 kDa for the hypocotyl enzyme]. Immunoblotanalysis also showed that particulate fractions from the endospermsand from etiolated and green cotyledons contained two catalasesubunits of 54 and 56 kDa, whereas such fractions from the hypocotylsand roots contained only the 56-kDa subunit. Leaf peroxisomesfrom green leaves had two catalase subunits of around 55 kDaeach. Results of translation in vitro indicated that the 54-and 56-kDa subunits were translated from distinct mRNAs andlevels of both mRNAs increased in the endosperms during germination,prior to increases in levels of catalase proteins. In the hypocotyls,the 56-kDa subunit seemed to be synthesized constitutively.
1Present addresses: YO, Toyota Central Institute, 31-9 Musashizuka,Nagabuchi, Nagakute, Aichi 480-11, Japan 相似文献
95.
Masao Suzuki Chizuru Tsuruoka Tatsuaki Kanai Takeshi Kato Fumio Yatagai Masami Watanabe 《Biological Sciences in Space》2003,17(4):302-306
We investigated the difference in cell-killing effect and mutation induction between carbon- and neon-ion beams in normal human cells. Carbon- and neon-ion beams were accelerated by the Riken Ring Cyclotron (RRC) at the Institute of Physical and Chemical Research in Japan. Cell-killing effect was measured as the reproductive cell death using the colony formation assay. Mutation induction at the HPRT locus was detected to measure 6-thioguanine-resistant clones. The mutation spectrum of the deletion pattern of exons of induced mutants was analyzed using the multiplex polymerase chain reaction (PCR). Cell-killing effect was almost the same between carbon- and neon-ion beams with similar linear energy transfer (LET) values, while there observed a large difference in mutation frequency. Furthermore, in the case of neon-ion beams 60% of mutants showed total deletions and 35-40% showed partial deletions, while 95-100% of carbon-ion induced mutants showed total deletions. The results suggest that different ion species may cause qualitative and quantitative difference in mutation induction even if the LET values are similar. 相似文献
96.
Takeshi Sagara Hiromu Egashira Mikako Okamura Ikuo Fujii Yasuyuki Shimohigashi Ken Kanematsu 《Bioorganic & medicinal chemistry》1996,4(12):2151-2166
For three-dimensional understanding of the mechanisms that control potency and selectivity of the ligand binding at the atomic level, we have analysed opioid receptor-ligand interaction based on the receptor's 3D model. As a first step, we have constructed molecular models for the multiple opioid receptor subtypes using bacteriorhodopsin as a template. The S-activated dihydromorphine derivatives should serve as powerful tools in mapping the three-dimensional structure of the μ opioid receptor, including the nature of the agonist-mediated conformational change that permits G protein-coupling to ‘second messenger’ effector molecules, and in identifying specific ligand-binding contacts with the μ opioid receptor. The analyses of the interactions of some opioid ligands with the predicted ligand binding sites are consistent with the results of the affinity labeling experiments. 相似文献
97.
Bacteria have devised sophisticated signaling systems for elicitinga variety of adaptive responses to their environment, whichare generally referred to as the "two-component regulatory system."The widespread occurrence of the two-component systems in bothprokaryotes and eukaryotes implies that it is a powerful devicefor a wide variety of adaptive responses of cells to their environment.The two-component signal transducers contain one or more ofthree conserved and characteristic phosphotransfer signalingdomains, named the "transmitter, receiver, and alternative transmitter."The recently determined entire genomic sequence of Synechocystissp. strain PCC 6803 allowed us to compile systematically a completelist of genes encoding such two-component signal transductionproteins. The results of such an effort, made in this study,revealed that at least 80 ORFs were identified as members ofthe two-component signal transducers in this single speciesof cyanobacteria. 相似文献
98.
Takeshi Nishimura Setsuko Yamamoto Takaaki Yamamoto Munekiyo Kaneko Youichi Hara 《Prostaglandins & other lipid mediators》1996,51(2):149-159
The antithrombotic effect of topical application of the 3-oxamethano-prostaglandin (PG) I1 analog, SM-10902 in the microcirculation and in vitro antiplatelet functions of its active form SM-10906 were estimated in comparison with PGI2 and PGE1. In rat platelets, SM-10906 evoked accumulation of intracellular cyclic adenosine 3′,5′-monophosphate, and exhibited antiaggregatory and disaggregatory activities, which were all enhanced by the phosphodiesterase inhibitor theophylline. Additionally, SM-10906 was shown to inhibit platelet adhesion to collagen in human platelet-rich plasma. PGI2 and PGE1 also showed in vitro antiplatelet effects in the order of PGI2 > SM-10906 ≥ PGE1. SM-10902 exhibited a dose-dependent antithrombotic effect in the guinea pig mesenteric arteriole by a topical application, and this activity might be exerted by the antiplatelet functions of SM-10906. Although SM-10906, PGI2 and PGE1 also showed the antithrombotic effects, SM-10902 was the most potent. In conclusion, the present studies indicate that an external topical preparation of SM-10902 may be useful for the therapy of peripheral circulatory insufficiency. 相似文献
99.
Minoru Kakeda Chiharu Ueguchi Hisami Yamada Takeshi Mizuno 《Molecular & general genetics : MGG》1995,248(5):629-634
100.
Seitaro Ohkuma Hidehiko Narihara Masashi Katsura Takeshi Hasegawa Kinya Kuriyama 《Journal of neurochemistry》1995,65(3):1109-1114
Abstract: The functional significance of peroxynitrite in the release of [3 H]GABA induced by nitric oxide (NO) liberated from NO generators was investigated using cerebral cortical neurons in primary culture. NO generators such as sodium nitroprusside (SNP) and S -nitroso- N -acetylpenicillamine (SNAP) increased [3 H]GABA release in a dose-dependent manner. These increases in [3 H]GABA release were significantly inhibited by hemoglobin, indicating that those NO generators evoke the release of [3 H]GABA by the formation of NO. Two types of superoxide scavengers, Cu2+ /Zn2+ superoxide dismutase and ceruloplasmin, significantly reduced the increase in [3 H]GABA release induced by both SNP and SNAP, which assumes that NO requires superoxide to induce [3 H]GABA release from the neurons. In addition, synthesized peroxynitrite induced a dose-dependent increase in [3 H]GABA release from the neurons. These results indicate that NO-induced [3 H]GABA release is mediated by peroxynitrite formed by the reaction of NO with superoxide. 相似文献