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991.
Yoshikawa M Matsuda H Morikawa T Xie H Nakamura S Muraoka O 《Bioorganic & medicinal chemistry》2006,14(22):7468-7475
The methanolic extract from the dried stems of Cistanche tubulosa (Schrenk) R. Wight was found to show an inhibitory effect on contractions induced by noradrenaline in isolated rat aortic strips. From the extract, new phenylethanoid oligoglycoside constituents, kankanosides F and G, and an acylated oligosugar, kankanose, were isolated together with 14 known compounds. The structures of these new compounds were determined on the basis of their chemical and physicochemical evidence. In addition, principal constituents, kankanoside F, kankanose, echinacoside, acteoside, and cistanoside F, showed vasorelaxant activity, and several structural requirements for the activity were clarified. 相似文献
992.
Yoshikawa M Nishida N Ninomiya K Ohgushi T Kubo M Morikawa T Matsuda H 《Bioorganic & medicinal chemistry》2006,14(2):456-463
The methanolic extract (200 mg/kg, p.o. and i.p.), principal coumarin constituents (isoepoxypteryxin, anomalin, and praeroside IV), and a polyacetylene constituent (falcarindiol) (25 mg/kg, i.p.) from the roots of Angelica furcijuga protected the liver injury induced by D-galactosamine (D-GalN)/lipopolysaccharide (LPS) in mice. In in vitro experiments, coumarin constituents (hyuganins A-D, anomalin, pteryxin, isopteryxin, and suksdorfin) and polyacetylene constituents [(-)-falcarinol and falcarindiol] substantially inhibited LPS-induced NO and/or TNF-alpha production in mouse peritoneal macrophages, and isoepoxypteryxin inhibited D-GalN-induced cytotoxicity in primary cultured rat hepatocytes. Furthermore, hyuganin A, anomalin, and isopteryxin inhibited the decrease in cell viability by TNF-alpha in L929 cells. 相似文献
993.
Currently there is no good hepatocyte model for studying growth hormone (GH) function that reflects its normal physiological roles. Here we report the establishment of a functional hepatocyte cell line, SDRL-1, from the liver of young male spontaneous dwarf rats (SDR), with isolated GH deficiency. This line has been maintained in Dulbecco's Modified Eagle Medium (DMEM)/F12 medium supplemented with 10% fetal bovine serum (FBS) with retention of a near diploid karyotype for extended periods of time. When grown as a monolayer sheet, it displayed a pavement-like appearance and contact inhibition. These cells have a poorly developed rough endoplasmic reticulum (r-ER), few mitochondria and glycogen granules, and produce a small amount of albumin and α-fetoprotein, that is enhanced when grown on a collagen gel sponge. Human recombinant GH stimulated JAK2 and STAT5b tyrosine phosphorylation and IGF-I production in a concentration-dependent manner. When the cells were cultured with GH-supplemented medium, the number of mitochondria and glycogen granules increased together with the r-ER and Golgi apparatus. A number of microvilli were observed on the surface of the cultured cells, further suggesting that this cell line is composed of normally functioning hepatocytes. In summary, we established a novel hepatocyte cell line (SDRL-1), that appears to display normal function, which we propose can serve as a good in vitro model for studying GH-target organ interactions. 相似文献
994.
There have been many reports suggesting that soluble oligomers of amyloid β (Aβ) are neurotoxins causing Alzheimer's disease (AD). Although inhibition of the soluble oligomerization of Aβ is considered to be effective in the treatment of AD, almost all peptide inhibitors have been designed from the β-sheet structure (H14-D23) of Aβ(1-42). To obtain more potent peptides than the known inhibitors of the soluble-oligomer formation of Aβ(1-42), we performed random screening by phage display. After fifth-round panning of a hepta-peptide library against soluble Aβ(1-42), novel peptides containing arginine residues were enriched. These peptides were found to suppress specifically 37/48 kDa oligomer formation and to keep the monomeric form of Aβ(1-42) even after 24 h of incubation, as disclosed by SDS-PAGE and size-exclusion chromatography. Thus we succeeded in acquiring novel efficient peptides for inhibition of soluble 37/48 kDa oligomer formation of Aβ(1-42). 相似文献
995.
Zhuo Xu Naoki Ichikawa Keisuke Kosaki Yoshihiko Yamada Takako Sasaki Lynn Y. Sakai Hisashi Kurosawa Nobutaka Hattori Eri Arikawa-Hirasawa 《Matrix biology》2010,29(6):461-470
Perlecan is a component of the basement membrane that surrounds skeletal muscle. The aim of the present study is to identify the role of perlecan in skeletal muscle hypertrophy and myostatin signaling, with and without mechanical stress, using a mouse model (Hspg2?/?-Tg) deficient in skeletal muscle perlecan. We found that myosin heavy chain (MHC) type IIb fibers in the tibialis anterior (TA) muscle of Hspg2?/?-Tg mice had a significantly increased fiber cross-sectional area (CSA) compared to control (WT-Tg) mice. Hspg2?/?-Tg mice also had an increased number of type IIx fibers in the TA muscle. Myostatin and its type I receptor (ALK4) expression was substantially decreased in the Hspg2?/?-Tg TA muscle. Myostatin-induced Smad activation was also reduced in a culture of myotubes from the Hspg2?/?-Tg muscle, suggesting that myostatin expression and its signaling were decreased in the Hspg2?/?-Tg muscle. To examine the effects of mechanical overload or unload on fast and slow muscles in Hspg2?/?-Tg mice, we performed tenotomy of the plantaris (fast) muscle and the soleus (slow) muscle. Mechanical overload on the plantaris muscle of Hspg2?/?-Tg mice significantly increased wet weights compared to those of control mice, and unloaded plantaris muscles of Hspg2?/?-Tg mice caused less decrease in wet weights compared to those of control mice. The decrease in myostatin expression was significantly profound in the overloaded plantaris muscle of Hspg2?/?-Tg mice, compared with that of control mice. In contrast, overloading the soleus muscle caused no changes in either type of muscle. These results suggest that perlecan is critical for maintaining fast muscle mass and fiber composition, and for regulating myostatin signaling. 相似文献
996.
Kohtaro Miyazawa Tetsuya Hondo Takashi Kanaya Sachi Tanaka Ikuro Takakura Wataru Itani Michael T. Rose Haruki Kitazawa Takahiro Yamaguchi Hisashi Aso 《Histochemistry and cell biology》2010,133(1):125-134
Membranous epithelial cells (M cells) of the follicle-associated epithelium in Peyer’s patches have a high capacity for transcytosis
of several viruses and microorganisms. Here, we report that we have successfully established a bovine intestinal epithelial
cell line (BIE cells) and developed an in vitro M cell model. BIE cells have a cobblestone morphology and microvilli-like
structures, and strongly express cell-to-cell junctional proteins and cytokeratin, which is a specific intermediate filament
protein of epithelial cells. After co-culture with murine intestinal lymphocytes or treatment with supernatant from bovine
PBMC cultured with IL-2, BIE cells acquired the ability of transcytosis. Therefore, BIE cells have typical characteristics
of bovine intestinal epithelial cells and also have the ability to differentiate into an M cell like linage. In addition,
our results indicate that contact between immune cells and epithelial cells may not be absolutely required for the differentiation
of M cells. We think that BIE cells will be useful for studying the transport mechanisms of various pathogens and also the
evaluation of drug delivery via M cells. 相似文献
997.
Midori Umekawa Takayuki Higashiyama Yurie Koga Tomonari Tanaka Masato Noguchi Atsushi Kobayashi Shin-ichiro Shoda Wei Huang Lai-Xi Wang Hisashi Ashida Kenji Yamamoto 《Biochimica et Biophysica Acta (BBA)/General Subjects》2010
Background
An efficient method for synthesizing homogenous glycoproteins is essential for elucidating the structural and functional roles of glycans of glycoproteins. We have focused on the transglycosylation activity of endo-β-N-acetylglucosaminidase from Mucor hiemalis (Endo-M) as a tool for glycoconjugate syntheses, since it can transfer en bloc the oligosaccharide of not only high-mannose type but also complex-type N-glycan onto various acceptors having an N-acetylglucosamine residue. However, there are two major bottlenecks for its practical application: the low yield of the transglycosylation product and the difficulty to obtain the activated sugar oxazoline substrate, especially the sialo-complex type one.Methods
We carried out the transglycosylation using a glycosynthase-like N175Q mutant of Endo-M, which was found to possess enhanced transglycosylation activity with sugar oxazoline as a donor substrate, in combination with an easy preparation of the sialo-complex-type sugar oxazoline from natural sialoglycopeptide in egg yolk.Results
Endo-M-N175Q showed efficient transglycosylation toward sialo-complex-type sugar oxazoline onto bioactive peptides and bovine ribonuclease B, and each sialylated compound was obtained in significantly high yield.Conclusions
Highly efficient and simple chemo-enzymatic syntheses of various sialylated compounds were enabled, by a combination of a simple synthesis of sialo-complex-type sugar oxazoline and the Endo-M-N175Q catalyzed transglycosylation.General significance
Our method would be very useful for a practical synthesis of biologically important glycopeptides and glycoproteins. 相似文献998.
Fumihiko Sato Asahi Ito Takashi Ishida Fumiko Mori Hisashi Takino Atsushi Inagaki Masaki Ri Shigeru Kusumoto Hirokazu Komatsu Shinsuke Iida Noriko Okada Hiroshi Inagaki Ryuzo Ueda 《Cancer immunology, immunotherapy : CII》2010,59(12):1791-1800
Engineering the Fc region of monoclonal antibodies (mAb) in order to enhance effector functions such as antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity (CDC) is likely to a be promising approach for next-generation mAb therapy. Here, we report on such an antibody, 113F, a novel CDC-enhancing variant of rituximab, and determine the tumor-associated factors influencing susceptibility to 113F-induced CDC. The latter included the quantity of complement inhibitors present, such as CD55 and CD59. We report that compared to rituximab, 113F mediated highly enhanced CDC against primary CD20-expressing lymphoma cells in vitro. Currently, a major problem in the field of immunotherapy research is the lack of suitable small animal models to evaluate human CDC in vivo. Therefore, we established a novel human tumor-bearing NOD/Shi-scid, IL-2Rγnull mouse model, in which human complement functions as the CDC mediator. We demonstrated that rituximab exerted significant antitumor effects via human CDC in this humanized mouse. The finding of specific localization of human C1q on CD20-expressing tumor cell membranes was consistent with the observation that human CDC indeed contributed to the antitumor effect in this model. Moreover, 113F exerted significantly more potent antitumor effects than rituximab in this in vivo model. The detection of more abundant dense signals from C1q using 113F compared to rituximab was consistent with the concept that this reagent represented a CDC-enhancing mAb. In the near future, the efficacy of this type of CDC-enhancing antibody will be determined in clinical trials in humans. 相似文献
999.
Yue Feng Sewon Kim Sang Yeol Lee Hisashi Koiwa 《Biochemical and biophysical research communications》2010,397(2):355-360
RNA polymerase II carboxyl-terminal domain (pol II CTD) phosphatases that can dephosphorylate both Ser2-PO4 and Ser5-PO4 of CTD have been identified in animals and yeasts, however, only Ser5-PO4-specific CTD phosphatases have been identified in plants. Among predicted Arabidopsis SCP1-like small phosphatases (SSP), SSP4, SSP4b, and SSP5 form a unique group with long N-terminal extensions. While SSPs’ expression showed similar tissue-specificities, SSP4 and SSP4b were localized exclusively in the nuclei, whereas SSP5 accumulated in both nuclei and cytoplasm. Detailed characterization of SSP activities using various peptides and full-length Arabidopsis pol II CTD substrates established that SSP4 and SSP4b could dephosphorylate both Ser2-PO4 and Ser5-PO4 of CTD, whereas SSP5 dephosphorylated only Ser5-PO4. These results indicate that Arabidopsis SSP gene family encodes active CTD phosphatases like animal SCP1 family proteins, with distinct substrate specificities. 相似文献
1000.