全文获取类型
收费全文 | 798篇 |
免费 | 45篇 |
出版年
2022年 | 4篇 |
2021年 | 4篇 |
2020年 | 5篇 |
2019年 | 6篇 |
2018年 | 8篇 |
2017年 | 8篇 |
2016年 | 10篇 |
2015年 | 22篇 |
2014年 | 27篇 |
2013年 | 32篇 |
2012年 | 38篇 |
2011年 | 29篇 |
2010年 | 26篇 |
2009年 | 14篇 |
2008年 | 34篇 |
2007年 | 32篇 |
2006年 | 32篇 |
2005年 | 31篇 |
2004年 | 37篇 |
2003年 | 43篇 |
2002年 | 42篇 |
2001年 | 50篇 |
2000年 | 39篇 |
1999年 | 29篇 |
1998年 | 11篇 |
1997年 | 18篇 |
1996年 | 5篇 |
1995年 | 10篇 |
1994年 | 7篇 |
1993年 | 3篇 |
1992年 | 13篇 |
1991年 | 16篇 |
1990年 | 6篇 |
1989年 | 9篇 |
1988年 | 11篇 |
1987年 | 15篇 |
1986年 | 10篇 |
1985年 | 12篇 |
1984年 | 7篇 |
1983年 | 11篇 |
1982年 | 9篇 |
1981年 | 7篇 |
1980年 | 8篇 |
1979年 | 8篇 |
1978年 | 8篇 |
1977年 | 7篇 |
1976年 | 7篇 |
1973年 | 5篇 |
1970年 | 4篇 |
1969年 | 4篇 |
排序方式: 共有843条查询结果,搜索用时 390 毫秒
751.
Kaito C Kai M Higo T Takayama E Fukamachi H Sekimizu K Shiokawa K 《Development, growth & differentiation》2001,43(4):383-390
752.
The anti-apoptotic protein BAG-3 is overexpressed in pancreatic cancer and induced by heat stress in pancreatic cancer cell lines 总被引:5,自引:0,他引:5
Liao Q Ozawa F Friess H Zimmermann A Takayama S Reed JC Kleeff J Büchler MW 《FEBS letters》2001,503(2-3):151-157
Pancreatic cancer cells are usually resistant to apoptosis mediated by intrinsic or extrinsic factors. BAG-3 (Bis, CAIR), which was identified as a BAG-1-related protein, is a novel modulator of cellular anti-apoptotic activity that functions through its interaction with Bcl-2. In this study we analyzed BAG-3 expression in human pancreatic cancer tissues and cell lines. BAG-3 mRNA was expressed at moderate to high levels in all pancreatic cancer samples, but at low levels in normal pancreas tissues. In situ hybridization and immunohistochemistry analysis revealed that BAG-3 was present in the cancer cells within the pancreatic tumor mass. When BAG-3 mRNA was analyzed in other gastrointestinal cancers (hepatocellular carcinoma; esophageal, stomach and colon cancer), no difference was found from their corresponding normal controls. In pancreatic cancer cells, BAG-3 mRNA expression levels were strongly induced after heat stress, but not in response to members of the tumor necrosis factor (TNF)-alpha family (TNF-alpha, TRAIL, FasL). These findings indicate that in pancreatic cancer, in contrast to other gastrointestinal malignancies, increased levels of BAG-3 might function to block apoptosis. This characteristic of pancreatic cancer might contribute to its more aggressive growth behavior and poor responsiveness to treatment in vivo. 相似文献
753.
Koji Takayama Daniel J. Crawford Patricio López-Sepúlveda Josef Greimler Tod F. Stuessy 《Journal of plant research》2018,131(3):469-485
Adaptive radiation is a common evolutionary phenomenon in oceanic islands. From one successful immigrant population, dispersal into different island environments and directional selection can rapidly yield a series of morphologically distinct species, each adapted to its own particular environment. Not all island immigrants, however, follow this evolutionary pathway. Others successfully arrive and establish viable populations, but they remain in the same ecological zone and only slowly diverge over millions of years. This transformational speciation, or anagenesis, is also common in oceanic archipelagos. The critical question is why do some groups radiate adaptively and others not? The Juan Fernández Islands contain 105 endemic taxa of angiosperms, 49% of which have originated by adaptive radiation (cladogenesis) and 51% by anagenesis, hence providing an opportunity to examine characteristics of taxa that have undergone both types of speciation in the same general island environment. Life form, dispersal mode, and total number of species in progenitors (genera) of endemic angiosperms in the archipelago were investigated from literature sources and compared with modes of speciation (cladogenesis vs. anagenesis). It is suggested that immigrants tending to undergo adaptive radiation are herbaceous perennial herbs, with leaky self-incompatible breeding systems, good intra-island dispersal capabilities, and flexible structural and physiological systems. Perhaps more importantly, the progenitors of adaptively radiated groups in islands are those that have already been successful in adaptations to different environments in source areas, and which have also undergone eco-geographic speciation. Evolutionary success via adaptive radiation in oceanic islands, therefore, is less a novel feature of island lineages but rather a continuation of tendency for successful adaptive speciation in lineages of continental source regions. 相似文献
754.
Ricardo José Dunder Anderson Luiz-Ferreira Ana Cristina Alves de Almeida Felipe Meira de-Faria Christiane Takayama Eduardo Augusto Rabelo Socca Marcos José Salvador Gláucia Coelho Mello Catarina dos Santos Pedro de Oliva-Neto Alba Regina Monteiro Souza-Brito 《Memórias do Instituto Oswaldo Cruz》2013,108(3):263-271
The present study evaluated the anti-inflammatory and analgesic properties of Agave sisalana Perrine in classic models of inflammation and pain. The hexanic fraction of A. sisalana (HFAS) was obtained by acid hydrolysis followed by hexanic reflux. Anti-inflammatory properties were examined in three acute mouse models (xylene ear oedema, hind paw oedema and pleurisy) and a chronic mouse model (granuloma cotton pellet). The antinociceptive potential was evaluated in chemical (acetic-acid) and thermal (tail-flick and hot-plate test) models of pain. When given orally, HFAS (5, 10, 25 and 50 mg/kg) reduced ear oedema (p < 0.0001; 52%, 71%, 62% and 42%, respectively). HFAS also reduced hind paw oedema at doses of 10 mg/kg and 25 mg/kg (p < 0.05; 42% and 58%, respectively) and pleurisy at doses of 10 mg/kg and 25 mg/kg (41% and 50%, respectively). In a chronic model, HFAS reduced inflammation by 46% and 58% at doses of 10 mg/kg and 25 mg/kg, respectively. Moreover, this fraction showed analgesic properties against the abdominal writhing in an acetic acid model (at doses of 5-25 mg/kg) with inhibitory rates of 24%, 54% and 48%. The HFAS also showed an increased latency time in the hot-plate (23% and 28%) and tail-flick tests (61% and 66%) for the 25 mg/kg and 50 mg/kg doses, respectively. These results suggest that HFAS has anti-inflammatory and analgesic properties. 相似文献
755.
Ryo Nakamura Masahiko Takayama Keisuke Nakamura Osamu Umemura 《Bioscience, biotechnology, and biochemistry》2013,77(10):2357-2362
A globulin fraction which was salted out from egg white by ammonium sulfate was constituted of five kinds of proteins. One of them was macroglobulin and two were G2 and G3 of Longsworth et al. [J. Am. Chem. Soc., 62, 2580 (1940)]. Remaining two proteins were assumed to be ovoinhibitors. G2 and G3 were separated from each other by CM-cellulose chromatography. The molecular weights of G2 and G3 were almost the same, being about 49,000. An euglobulin-like protein which was precipitated during the dialysis of the globulin fraction consisted mainly of macroglobulin and aggregates of some other egg white proteins. 相似文献
756.
Naoto Fujiwara Ryosuke Tateishi Masaaki Akahane Masataka Taguri Tatsuya Minami Shintaro Mikami Masaya Sato Kouji Uchino Kenichiro Enooku Yuji Kondo Yoshinari Asaoka Noriyo Yamashiki Tadashi Goto Shuichiro Shiina Haruhiko Yoshida Kuni Ohtomo Kazuhiko Koike 《PloS one》2013,8(10)
Background
To elucidate whether repeated exposures to iodinated contrast media increase the risk of adverse reaction.Materials and Methods
We retrospectively reviewed 1,861 patients with hepatocellular carcinoma who visited authors’ institution, a tertiary referral center, between 2004 and 2008. We analyzed cumulative probability of adverse reactions and risk factors. We categorized all symptoms into hypersensitivity reactions, physiologic reactions, and other reactions, according to the American College of Radiology guidelines, and evaluated each category as an event. We estimated the association between hazard for adverse reactions and the number of cumulative exposures to contrast media. We also evaluated subsequent contrast media injections and adverse reactions.Results
There were 23,684 contrast media injections in 1,729 patients. One hundred and thirty-two patients were excluded because they were given no contrast media during the study period. Adverse reactions occurred in 196 (0.83%) patients. The cumulative incidence at 10th, 20th, and 30th examination was 7.9%, 15.2%, and 24.1%, respectively. Presence of renal impairment was found to be one of risk factors for adverse reactions. The estimated hazard of overall adverse reaction gradually decreased until around 10th exposure and rose with subsequent exposures. The estimated hazard of hypersensitivity showed V-shaped change with cumulative number of exposures. The estimated hazard of physiologic reaction had a tendency toward decreasing and that of other reaction had a tendency toward increasing. Second adverse reaction was more severe than the initial in only one among 130 patients receiving subsequent injections.Conclusion
Repeated exposures to iodinated contrast media increase the risk of adverse reaction. 相似文献757.
Kaiga T Sato M Kaneda H Iwakura Y Takayama T Tahara H 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(12):7571-7580
IL-23, a cytokine, which is composed of the p40 subunit shared with IL-12 and the IL-23-specific p19 subunit, has been shown to preferentially act on Th1 effector/memory CD4+ T cells and to induce their proliferation and IFN-gamma production. The IL-23 is also reported to act on Th17-CD4+ T cells, which are involved in inducing tissue injury. In this study, we examined the antitumor effects associated with systemic administration of IL-23 and their mechanisms in mouse tumor system. Systemic administration of high-dose IL-23 was achieved using in vivo electroporation of IL-23 plasmid DNA into the pretibial muscles of C57BL/6 mice. The IL-23 treatment was associated with significant suppression of the growth of pre-existing MCA205 fibrosarcoma and prolongation of the survival of treated mice without significant toxicity when compared with those of the mice treated with EGFP. Although the therapeutic outcomes were similar to those with the IL-12 treatment, the IL-23 treatment induced characteristic immune responses distinctive to those of IL-12 treatment. The IL-23 administration even at the therapeutic levels did not induce detectable IFN-gamma concentration in the serum. In vivo depletion of CD4+ T cells, CD8+ T cells, or NK cells significantly inhibited the antitumor effects of IL-23. Furthermore, the CD4+ T cells in the lymph nodes in the IL-23-treated mice showed significant IFN-gamma and IL-17 response upon anti-CD3 mAb stimulation in vitro. These results and the ones in the IFN-gamma or IL-12 gene knockout mice suggest that potent antitumor effects of IL-23 treatment could be achieved when the Th1-type response is fully promoted in the presence of endogenously expressed IL-12. 相似文献
758.
Sphingosine 1-phosphate-mediated trafficking of pathogenic Th2 and mast cells for the control of food allergy 总被引:1,自引:0,他引:1
Kurashima Y Kunisawa J Higuchi M Gohda M Ishikawa I Takayama N Shimizu M Kiyono H 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(3):1577-1585
Sphingosine 1-phosphate (S1P) has been proposed as a regulator of lymphocyte trafficking, but its role in mucosa-associated diseases, such as in food allergies, remains to be elucidated. To examine the role of S1P in allergic diseases in the intestine, we used a Th2 cell-mediated Ag-specific allergic diarrhea model and demonstrated that type 1 S1P receptor (S1P(1)) expression was preferentially associated with pathogenic CD4(+) T cells for the development of allergic reactions. Consistent with this demonstration, treatment with FTY720, a modulator of the S1P(1), prevented allergic diarrhea by inhibiting the migration of systemically primed pathogenic CD4(+) T cells induced by oral challenge with allergen into the large intestine. In addition, FTY720 hampered mast cell infiltration into the large intestine, whereas eosinophil infiltration into the large intestine and total and allergen-specific serum IgE production were comparable between mock- and FTY720-treated groups. These results suggest that modulation of the S1P-mediated pathway to inhibit the migration of pathogenic CD4(+) T cells and mast cells into the large intestine could be a novel strategy for preventing allergic diarrhea. 相似文献
759.
Iwano M Shiba H Matoba K Miwa T Funato M Entani T Nakayama P Shimosato H Takaoka A Isogai A Takayama S 《Plant physiology》2007,144(1):72-81
The self-incompatibility system of the plant species Brassica is controlled by the S-locus, which contains S-RECEPTOR KINASE (SRK) and S-LOCUS PROTEIN11 (SP11). SP11 binding to SRK induces SRK autophosphorylation and initiates a signaling cascade leading to the rejection of self pollen. However, the mechanism controlling hydration and germination arrest during self-pollination is unclear. In this study, we examined the role of actin, a key cytoskeletal component regulating the transport system for hydration and germination in the papilla cell during pollination. Using rhodamine-phalloidin staining, we showed that cross-pollination induced actin polymerization, whereas self-pollination induced actin reorganization and likely depolymerization. By monitoring transiently expressed green fluorescent protein fused to the actin-binding domain of mouse talin, we observed the concentration of actin bundles at the cross-pollen attachment site and actin reorganization and likely depolymerization at the self-pollen attachment site; the results correspond to those obtained by rhodamine-phalloidin staining. We further showed that the coat of self pollen is sufficient to mediate this response. The actin-depolymerizing drug cytochalasin D significantly inhibited pollen hydration and germination during cross-pollination, further emphasizing a role for actin in these processes. Additionally, three-dimensional electron microscopic tomography revealed the close association of the actin cytoskeleton with an apical vacuole network. Self-pollination disrupted the vacuole network, whereas cross-pollination led to vacuolar rearrangements toward the site of pollen attachment. Taken together, our data suggest that self- and cross-pollination differentially affect the dynamics of the actin cytoskeleton, leading to changes in vacuolar structure associated with hydration and germination. 相似文献
760.
Yarita K Sano A Murata Y Takayama A Takahashi Y Takahashi H Yaguchi T Ohori A Kamei K Miyaji M Nishimura K 《Mycopathologia》2007,164(3):135-147
Four strains of Ochroconis gallopava from 3 out of 15 Japanese hot springs were isolated. Colonies of the hot spring isolates were uniformly floccose and dark
olive green on the surface and dark brown on their reverse side on potato dextrose agar (PDA) plates, however, they became
felty, flat, and brownish-black, and produced a reddish-brown pigment after several times of subculture at room temperature.
Shapes and sizes of conidia of the four strains were individual, while the D1/D2 domain of the large subunit ribosomal RNA
gene sequences showed 99.7% identity in the GenBank database. The DNA pattern of the hot spring isolates amplified by species
specific loop mediated isothermal amplification method were as the same pattern as that of a clinical isolate. The minimum
inhibitory concentrations of antifungal agents to O. gallopava isolated from the hot springs were ranged from 0.5 to 1 μg/ml in amphotericin B, 1 to 16 μg/ml in flucytosine, 0.125 to 0.25 μg/ml
in itraconazole, 1 to 4 μg/ml in miconazole, 16 to 64 μg/ml in flconazole and 0.03 to 0.5 μg/ml in micafungin. The isolates
had fatal outcome in experimentally infected mice intravenously with severe invasiveness to brains and kidneys. These findings
suggested that O. gallopava habitats in hot springs could be one of sources for infection. 相似文献