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991.
Hiroshi Yamamoto Kazuhisa Maeda Yoshitaka Uji Hiroshi Tsuchihashi Tsuyoshi Mori Tomoharu Shimizu Yoshihiro Endo Aya Kadota Katsuyuki Miura Yusuke Koga Toshinori Ito Tohru Tani 《PloS one》2013,8(3)
Background and Purpose
Infections are important causes of postoperative morbidity after gastric surgery; currently, no factors have been identified that can predict postoperative infection. Adiponectin (ADN) mediates energy metabolism and functions as an immunomodulator. Perioperative ADN levels and perioperative immune functioning could be mutually related. Here we evaluated a potential biological marker to reliably predict the incidence of postoperative infections to prevent such comorbidities.Methods
We analyzed 150 consecutive patients who underwent elective gastric cancer surgery at the Shiga University of Medical Science Hospital (Shiga, Japan) from 1997 to 2009; of these, most surgeries (n = 100) were performed 2008 onwards. The patient characteristics and surgery-related factors between two groups (with and without infection) were compared by the paired t-test and χ2 test, including preoperative ADN levels, postoperative day 1 ADN levels, and ADN ratio (postoperative ADN levels/preoperative ADN levels) as baseline factors. Logistic regression analysis was performed to access the independent association between ADN ratio and postoperative infection. Finally, receiver operating curves (ROCs) were constructed to examine its clinical utility.Results
Sixty patients (40%) experienced postoperative infections. The baseline values of age, American Society of Anesthesiologists physical status, total operating time, blood loss, surgical procedure, C-reactive protein (CRP) levels, preoperative ADN levels, and ADN ratio were significantly different between groups. Logistic regression analysis using these factors indicated that type 2 diabetes mellitus (T2DM) and ADN ratio were significantly independent variables (*p<0.05, ** p<0.01, respectively). ROC analysis revealed that the useful cutoff values (sensitivity/specificity) for preoperative ADN levels, ADN ratio, blood loss, operating time, and CRP levels were 8.81(0.567/0.568), 0.76 (0.767/0.761), 405 g (0.717/0.693), 342 min (0.617/0.614), and 8.94 mg/dl (0.583/0.591), respectively.Conclusion
T2DM and ADN ratio were independent predictors of postoperative infection and ADN ratio was the most useful predictor for postoperative infection. 相似文献992.
Shohei Shinozaki Tsuyoshi Chiba Koichi Kokame Toshiyuki Miyata Eiji Kaneko Kentaro Shimokado 《PloS one》2013,8(10)
Herp was originally identified as an endoplasmic reticulum (ER) stress protein in vascular endothelial cells. ER stress is induced in atherosclerotic lesions, but it is not known whether Herp plays any role in the development of atherosclerosis. To address this question, we generated Herp- and apolipoprotein E (apoE)-deficient mice (Herp−/−; apoE−/− mice) by crossbreeding Herp−/− mice and apoE−/− mice. Herp was expressed in the endothelial cells and medial smooth muscle cells of the aorta, as well as in a subset of macrophages in the atherosclerotic lesions in apoE−/− mice, while there was no expression of Herp in the Herp−/−; apoE−/− mice. The doubly deficient mice developed significantly fewer atherosclerotic lesions than the apoE−/− mice at 36 and 72 weeks of age, whereas the plasma levels of cholesterol and triglycerides were not significantly different between the strains. The plasma levels of non-esterified fatty acids were significantly lower in the Herp−/−; apoE−/− mice when they were eight and 16 weeks old. The gene expression levels of ER stress response proteins (GRP78 and CHOP) and inflammatory cytokines (IL-1β, IL-6, TNF-α and MCP-1) in the aorta were significantly lower in Herp−/−; apoE−/− mice than in apoE−/− mice, suggesting that Herp mediated ER stress-induced inflammation. In fact, peritoneal macrophages isolated from Herp-deficient mice and RAW264.7 macrophages in which Herp was eliminated with a siRNA expressed lower levels of mRNA for inflammatory cytokines when they were treated with tunicamycin. Herp deficiency affected the major mediators of the unfolded protein response, including IRE1 and PERK, but not ATF6. These findings suggest that a deficiency of Herp suppressed the development of atherosclerosis by attenuating the ER stress-induced inflammatory reactions. 相似文献
993.
Takafumi Kuroda Yoshihiko Hirohashi Toshihiko Torigoe Kazuyo Yasuda Akari Takahashi Hiroko Asanuma Rena Morita Tasuku Mariya Takuya Asano Masahito Mizuuchi Tsuyoshi Saito Noriyuki Sato 《PloS one》2013,8(6)
Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined as a small population of cancer cells that have high tumorigenicity. Furthermore, CSCs/CICs are resistant to several cancer therapies, and CSCs/CICs are therefore thought to be responsible for cancer recurrence after treatment and distant metastasis. In epithelial ovarian cancer (EOC) cases, disease recurrence after chemotherapy is frequently observed, suggesting ovarian CSCs/CICs are involved. There are four major histological subtypes in EOC, and serous adenocarcinoma and clear cell adenocarcinoma are high-grade malignancies. We therefore analyzed ovarian CSCs/CICs from ovarian carcinoma cell lines (serous adenocarcinoma and clear cell adenocarcinoma) and primary ovarian cancer cells in this study. We isolated ovarian CSCs/CICs as an aldehyde dehydrogenase 1 high (ALDH1high) population from 6 EOC cell lines (3 serous adenocarcinomas and 3 clear cell adenocarcinomas) by the ALDEFLUOR assay. ALDH1high cells showed greater sphere-forming ability, higher tumorigenicity and greater invasive capability, indicating that ovarian CSCs/CICs are enriched in ALDH1high cells. ALDH1high cells could also be isolated from 8 of 11 primary ovarian carcinoma samples. Immunohistochemical staining revealed that higher ALDH1 expression levels in ovary cancer cases are related to poorer prognosis in both serous adenocarcinoma cases and clear cell adenocarcinoma cases. Taken together, the results indicate that ALDH1 is a marker for ovarian CSCs/CICs and that the expression level of ALDH1 might be a novel biomarker for prediction of poor prognosis. 相似文献
994.
Nobuhiko Wada Toshihiko Hashinaga Shuichi Otabe Xiaohong Yuan Yayoi Kurita Satomi Kakino Tsuyoshi Ohoki Hitomi Nakayama Tomoka Fukutani Yuji Tajiri Kentaro Yamada 《PloS one》2013,8(7)
Background
Adiponectin-transgenic mice had many small adipocytes in both subcutaneous and visceral adipose tissues, and showed higher sensitivity to insulin, longer life span, and reduced chronic inflammation. We hypothesized that adiponectin regulates Wnt signaling in adipocytes and thereby modulates adipocyte proliferation and chronic inflammation in adipose tissue.Materials and Methods
We examined the expression of all Wnt ligands and their receptors and the activity of Wnt signaling pathways in visceral adipose tissue from wild-type mice and two lines of adiponectin-transgenic mice. The effects of adiponectin were also investigated in cultured 3T3-L1 cells.Results
The Wnt5b, Wnt6, Frizzled 6 (Fzd6), and Fzd9 genes were up-regulated in both lines of transgenic mice, whereas Wnt1, Wnt2, Wnt5a, Wnt9b, Wnt10b, Wnt11, Fzd1, Fzd2, Fzd4, Fzd7, and the Fzd coreceptor low-density-lipoprotein receptor-related protein 6 (Lrp6) were reduced. There was no difference in total β-catenin levels in whole-cell extracts, non-phospho-β-catenin levels in nuclear extracts, or mRNA levels of β-catenin target genes, indicating that hyperadiponectinemia did not affect canonical Wnt signaling. In contrast, phosphorylated calcium/calmodulin-dependent kinase II (p-CaMKII) and phosphorylated Jun N-terminal kinase (p-JNK) were markedly reduced in adipose tissue from the transgenic mice. The adipose tissue of the transgenic mice consisted of many small cells and had increased expression of adiponectin, whereas cyclooxygenase-2 expression was reduced. Wnt5b expression was elevated in preadipocytes of the transgenic mice and decreased in diet-induced obese mice, suggesting a role in adipocyte differentiation. Some Wnt genes, Fzd genes, and p-CaMKII protein were down-regulated in 3T3-L1 cells cultured with a high concentration of adiponectin.Conclusion
Chronic hyperadiponectinemia selectively modulated the expression of Wnt ligands, Fzd receptors and LRP coreceptors accompanied by the inhibition of the Wnt/Ca2+ and JNK signaling pathways, which may be involved in the altered adipocyte cellularity, endogenous adiponectin production, and anti-inflammatory action induced by hyperadiponectinemia. 相似文献995.
Sachi Tsunemi Tsuyoshi Iwasaki Sachie Kitano Kunio Matsumoto Misato Takagi-Kimura Shuji Kubo Tomoko Tamaoki Hajime Sano 《Arthritis research & therapy》2013,15(4):R75
Introduction
Hepatocyte growth factor (HGF) is a potent proangiogenic molecule that induces neovascularization. The HGF antagonist, NK4, competitively antagonizes HGF binding to its receptor. In the present study, we determined the inhibitory effect of NK4 in a rheumatoid arthritis (RA) model using SKG mice.Methods
Arthritis was induced in SKG mice by a single intraperitoneal injection of β-glucan. Recombinant adenovirus containing NK4 cDNA (AdCMV.NK4) was also injected intravenously at the time of or 1 month after β-glucan injection. Ankle bone destruction was examined radiographically. The histopathologic features of joints were examined using hematoxylin and eosin and immunohistochemical staining. Enzyme-linked immunosorbent assays were used to determine the serum levels of HGF, interferon γ (IFN-γ, interleukin 4 (IL-4) and IL-17 production by CD4+ T cells stimulated with allogeneic spleen cells.Results
The intravenous injection of AdCMV.NK4 into SKG mice suppressed the progression of β-glucan-induced arthritis. Bone destruction was also inhibited by NK4 treatment. The histopathologic findings of the ankles revealed that angiogenesis, inflammatory cytokines and RANKL expression in synovial tissues were significantly inhibited by NK4 treatment. Recombinant NK4 (rNK4) proteins inhibited IFN-γ, IL-4 and IL-17 production by CD4+ T cells stimulated with allogeneic spleen cells.Conclusions
These results indicate that NK4 inhibits arthritis by inhibition of angiogenesis and inflammatory cytokine production by CD4+ T cells. Therefore, molecular targeting of angiogenic inducers by NK4 can potentially be used as a novel therapeutic approach for the treatment of RA. 相似文献996.
Tsuyoshi HOSOYA Yukiko SAITO Yukio HARADA Kazuaki TANAKA Yan-Jie ZHAO Makoto KAKISHIMA 《菌物学报》2013,32(3):448-456
对日本新记录种Stamnaria americana进行了描述和图示。尽管低温适宜该种子囊孢子的萌发,它在20℃生长最好。DNA序列分析的结果表明,其分类地位应该从柔膜菌科转入锤舌菌科。 相似文献
997.
Masahiro Kuroda Shintaro Funasaki Tsuyoshi Saitoh Yukiko Sasazawa Shigeru Nishiyama Kazuo Umezawa Siro Simizu 《FEBS letters》2013
Conophylline (CNP) has various biological activities, such as insulin production. A recent study identified ADP-ribosylation factor-like 6-interacting protein 1 (ARL6ip1) as a direct target protein of CNP. In this study, we revealed that ARL6ip1 is a three-spanning transmembrane protein and determined the CNP-binding domain of ARL6ip1 by deletion mutation analysis of ARL6ip1 with biotinyl-amino-CNP. These results suggest that CNP is expected to be useful for future investigation of ARL6ip1 function in cells. Because of the anti-apoptotic function of ARL6ip1, CNP may be an effective therapeutic drug and/or a novel chemosensitizer for human cancers and other diseases. 相似文献
998.
Masakazu Kogawa Koji Hisatake Gerald J. Atkins David M. Findlay Yuichiro Enoki Tsuyoshi Sato Peter C. Gray Yukiko Kanesaki-Yatsuka Paul H. Anderson Seiki Wada Naoki Kato Aya Fukuda Shigehiro Katayama Masafumi Tsujimoto Tetsuya Yoda Tatsuo Suda Yasushi Okazaki Masahito Matsumoto 《The Journal of biological chemistry》2013,288(43):31299-31312
999.
Point Mutation in Syntaxin-1A Causes Abnormal Vesicle Recycling,Behaviors, and Short Term Plasticity
Yumi Watanabe Norikazu Katayama Kosei Takeuchi Tetsuya Togano Rieko Itoh Michiko Sato Maya Yamazaki Manabu Abe Toshiya Sato Kanako Oda Minesuke Yokoyama Keizo Takao Masahiro Fukaya Tsuyoshi Miyakawa Masahiko Watanabe Kenji Sakimura Toshiya Manabe Michihiro Igarashi 《The Journal of biological chemistry》2013,288(48):34906-34919
Syntaxin-1A is a t-SNARE that is involved in vesicle docking and vesicle fusion; it is important in presynaptic exocytosis in neurons because it interacts with many regulatory proteins. Previously, we found the following: 1) that autophosphorylated Ca2+/calmodulin-dependent protein kinase II (CaMKII), an important modulator of neural plasticity, interacts with syntaxin-1A to regulate exocytosis, and 2) that a syntaxin missense mutation (R151G) attenuated this interaction. To determine more precisely the physiological importance of this interaction between CaMKII and syntaxin, we generated mice with a knock-in (KI) syntaxin-1A (R151G) mutation. Complexin is a molecular clamp involved in exocytosis, and in the KI mice, recruitment of complexin to the SNARE complex was reduced because of an abnormal CaMKII/syntaxin interaction. Nevertheless, SNARE complex formation was not inhibited, and consequently, basal neurotransmission was normal. However, the KI mice did exhibit more enhanced presynaptic plasticity than wild-type littermates; this enhanced plasticity could be associated with synaptic response than did wild-type littermates; this pronounced response included several behavioral abnormalities. Notably, the R151G phenotypes were generally similar to previously reported CaMKII mutant phenotypes. Additionally, synaptic recycling in these KI mice was delayed, and the density of synaptic vesicles was reduced. Taken together, our results indicated that this single point mutation in syntaxin-1A causes abnormal regulation of neuronal plasticity and vesicle recycling and that the affected syntaxin-1A/CaMKII interaction is essential for normal brain and synaptic functions in vivo. 相似文献