全文获取类型
收费全文 | 10053篇 |
免费 | 572篇 |
出版年
2021年 | 106篇 |
2020年 | 57篇 |
2019年 | 82篇 |
2018年 | 116篇 |
2017年 | 114篇 |
2016年 | 188篇 |
2015年 | 274篇 |
2014年 | 294篇 |
2013年 | 576篇 |
2012年 | 472篇 |
2011年 | 504篇 |
2010年 | 297篇 |
2009年 | 311篇 |
2008年 | 465篇 |
2007年 | 458篇 |
2006年 | 405篇 |
2005年 | 450篇 |
2004年 | 418篇 |
2003年 | 428篇 |
2002年 | 401篇 |
2001年 | 362篇 |
2000年 | 388篇 |
1999年 | 283篇 |
1998年 | 131篇 |
1997年 | 97篇 |
1996年 | 67篇 |
1995年 | 83篇 |
1994年 | 79篇 |
1993年 | 93篇 |
1992年 | 201篇 |
1991年 | 206篇 |
1990年 | 208篇 |
1989年 | 195篇 |
1988年 | 181篇 |
1987年 | 149篇 |
1986年 | 121篇 |
1985年 | 117篇 |
1984年 | 118篇 |
1983年 | 91篇 |
1982年 | 85篇 |
1981年 | 71篇 |
1979年 | 87篇 |
1978年 | 66篇 |
1977年 | 64篇 |
1976年 | 63篇 |
1975年 | 61篇 |
1974年 | 64篇 |
1973年 | 57篇 |
1972年 | 65篇 |
1971年 | 48篇 |
排序方式: 共有10000条查询结果,搜索用时 983 毫秒
991.
Yasuhiro Ohshima Mitsutoshi Tsukimoto Takato Takenouchi Hitoshi Harada Akina Suzuki Mitsuru Sato Hiroshi Kitani Shuji Kojima 《Biochimica et Biophysica Acta (BBA)/General Subjects》2010
Background
Ionizing irradiation causes not only growth arrest and cell death, but also release of growth factors or signal transmitters, which promote cancer malignancy. Extracellular ATP controls cancer growth through activation of purinoceptors. However, there is no report of radiation-induced ATP release from cancer cells. Here, we examined γ-irradiation-induced ATP release and its mechanism in B16 melanoma.Methods
Extracellular ATP was measured by luciferin–luciferase assay. To investigate mechanism of radiation-induced ATP release, we pharmacologically inhibited the ATP release and established stable P2X7 receptor-knockdown B16 melanoma cells using two short hairpin RNAs targeting P2X7 receptor.Results
Cells were exposed to 0.5–8 Gy of γ-rays. Extracellular ATP was increased, peaking at 5 min after 0.5 Gy irradiation. A selective P2X7 receptor channel antagonist, but not anion transporter inhibitors, blocked the release of ATP. Further, radiation-induced ATP release was significantly decreased in P2X7 receptor-knockdown cells. Our results indicate that γ-irradiation evokes ATP release from melanoma cells, and P2X7 receptor channel plays a significant role in mediating the ATP release.General Significance
We suggest that extracellular ATP could be a novel intercellular signaling molecule released from cancer cells when cells are exposed to ionizing radiation. 相似文献992.
Masakatsu Kamiya Keisuke Oyauchi Yoshinori Sato Takuya Yokoyama Mofei Wang Tomoyasu Aizawa Yasuhiro Kumaki Mineyuki Mizuguchi Kunio Imai Makoto Demura Koichi Suzuki Keiichi Kawano 《Journal of peptide science》2010,16(5):242-248
We previously reported that yamamarin, a pentapeptide with an amidated C‐terminus (DILRG‐NH2) isolated from larvae of the silkmoth, and its palmitoylated analog (C16‐DILRG‐NH2) suppressed proliferation of rat hepatoma (liver cancer) cells. In this study, we investigated the structure–activity relationship of yamamarin by in vitro assay and spectroscopic methods (CD and NMR) for various analogs. The in vitro assay results demonstrated that the chemical structure of the C‐terminal part (‐RG‐NH2) of yamamarin is essential for its activity. The CD and NMR results indicated that yamamarin and its analog adopt predominantly a random coil conformation. Moreover, a comparison of NMR spectra of DILRG‐NH2 and C16‐DILRG‐NH2 revealed that the N‐terminal palmitoyl group of C16‐DILRG‐NH2 did not affect the conformation of the C‐terminal part, which is essential for activity. Together, these results should assist in the design of more sophisticated anticancer drugs. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
993.
Gordon H. Sato J. Denry Sato Tetsuji Okamoto Wallace L. McKeehan David W. Barnes 《In vitro cellular & developmental biology. Animal》2010,46(7):590-594
Lack of tissue-specific differentiated functions of cells in tissue culture, once thought to be due to “dedifferentiation”,
was shown to be due to selective overgrowth of fibroblasts by a series of simple experiments that challenged the prevailing
dogma. Following this insight, enrichment culture techniques (alternate animal and culture passage) were designed to give
functionally differentiated tumor cells selective advantage over the fibroblasts. These experiments resulted in the derivation
of a large number of functionally differentiated clonal strains of a range of cell types, providing the final point of destruction
of the dogma of “dedifferentiation.” Instead, the hypothesis was proposed that cells in culture accurately represent cells
in vivo, but without the complex in vivo environment. With the development of hormonally defined media and its combination
with functionally differentiated clonal cell lines, this concept has been strengthened and the potential of tissue culture
studies has been greatly augmented. Hormonally defined media allow the culture of cell types that cannot be grown in conventional,
serum-supplemented media. These approaches demonstrate that hormonal responses and dependencies can be discovered in culture.
Following this thinking and the discovery of hormonal dependencies of cancer cells has led to a new rationale for therapy.
Tissue culture and cell technology continue to play an important role in solving human health problems. 相似文献
994.
Kanazuru T Sato EF Nagata K Matsui H Watanabe K Kasahara E Jikumaru M Inoue J Inoue M 《Journal of microbiology (Seoul, Korea)》2010,48(6):778-783
Some gastrointestinal bacteria synthesize hydrogen (H2) by fermentation. Despite the presence of bactericidal factors in human saliva, a large number of bacteria also live in the
oral cavity. It has never been shown that oral bacteria also produce H2 or what role H2 might play in the oral cavity. It was found that a significant amount of H2 is synthesized in the oral cavity of healthy human subjects, and that its generation is enhanced by the presence of glucose
but inhibited by either teeth brushing or sterilization with povidone iodine. These observations suggest the presence of H2-generating bacteria in the oral cavity. The screening of commensal bacteria in the oral cavity revealed that a variety of
anaerobic bacteria generate H2. Among them, Klebsiella pneumoniae (K. pneumoniae) generated significantly large amounts of H2 in the presence of glucose. Biochemical analysis revealed that various proteins in K. pneumoniae are carbonylated under standard culture conditions, and that oxidative stress induced by the presence of Fe++ and H2O2 increases the number of carbonylated proteins, particularly when their hydrogenase activity is inhibited by KCN. Inhibition
of H2 generation markedly suppresses the growth of K. pneumoniae. These observations suggest that H2 generation and/or the reduction of oxidative stress is important for the survival and growth of K. pneumoniae in the oral cavity. 相似文献
995.
996.
The clinical significance of glutathione-S-transferase GSTM1, GSTT1 and p53 codon 72 polymorphisms in cervical carcinogenesis was investigated. Germline polymorphisms of GSTM1, GSTT1 and p53 codon 72 together with human papillomavirus (HPV) types were examined in a total of 457 blood and cervical smear samples from normal healthy women and the patients with premalignant and malignant cervical lesions. The 167 patients with low-grade squamous intraepithelial lesion (LSIL), 49 with high-grade SIL (HSIL) and 83 with squamous cell carcinoma (SCC) had significantly higher frequency of high-risk HPV than 158 controls. The 49 patients with HSIL and 83 with SCC had statistically higher frequency of null GSTT1 genotype than 158 controls. There was an increased odds ratio for null GSTT1 genotype in HSIL and SCC cases compared with controls among 191 patients with high-risk HPV. The 67 cases with HPV types 16 and/or 18 had higher frequency of the GSTT1 null genotype than 186 with other types of HPV. There was no statistical difference in the polymorphic frequency of GSTM1 and p53 codon 72 genotypes between SILs and controls with or without high-risk HPV. These results suggest that GSTT1 null genotype may increase the risk of cervical cancer particularly in the cases with high-risk HPV types in a Japanese population. 相似文献
997.
998.
Y. Sato S. Miyai D. Haraguchi S. Ohno T. Kohama K. Kawamura M. Yamagishi 《Journal of Applied Entomology》2010,134(4):303-312
The West Indian sweetpotato weevil Euscepes postfasciatus (Fairmaire) is a major pest of the sweet potato Ipomoea batatas (L.) Lam. and this weevil is a target of an eradication program using the Sterile Insect Technique in Okinawa Prefecture, Japan. Understanding the population ecology is essential in the planning of an eradication program; hence, a host‐plant infestation survey and light trap survey have been conducted to monitor the population dynamics of the weevil on Kume Island (Okinawa Prefecture), which is the target area of the trial weevil eradication project. Seasonal tendencies of weevil density were found in these field surveys, but the tendency found in the host‐plant infestation survey was not seen every year, and the effectiveness of the light trap is somewhat suspect. To confirm the reliability of the tendency observed in these field surveys, the present study attempted to explain the tendency by a seasonal temperature change using a temperature‐based model of weevil population dynamics. The seasonal changes of weevil density differed according to host plants and host‐plant fields. The seasonal changes of weevil density inside the host plant Ipomoea indica and outside the host plants in I. indica fields were consistent with those predicted by the model. However, those inside the host plant Ipomoea pes‐caprae in the host‐plant infestation survey were contrary to the predicted ones, and those observed outside host plants in I. pes‐caprae fields by the light trap survey were not in good agreement with the predicted ones. It was concluded that the seasonal change of the weevil density observed in I. indica and I. indica fields can be explained by a seasonal temperature change, but factors other than seasonal temperature change are needed to explain those in I. pes‐caprae and I. pes‐caprae fields. 相似文献
999.
Pyrrole derivatives as potent inhibitors of lymphocyte-specific kinase: Structure,synthesis, and SAR
Tetsuo Takayama Hiroki Umemiya Hideaki Amada Tetsuya Yabuuchi Fumiyasu Shiozawa Hironori Katakai Akiko Takaoka Akie Yamaguchi Mayumi Endo Masakazu Sato 《Bioorganic & medicinal chemistry letters》2010,20(1):108-111
We have described the synthesis, enzyme inhibitory activity, structure–activity relationships, and proposed binding mode of a novel series of pyrrole derivatives as lymphocyte-specific kinase (Lck) inhibitors. The most potent analogs exhibited good enzyme inhibitory activity (IC50s <10 nM) for Lck kinase inhibition. 相似文献
1000.
Masaki Asada Tetsuo Obitsu Atsushi Kinoshita Yoshihiko Nakai Toshihiko Nagase Isamu Sugimoto Motoyuki Tanaka Hiroya Takizawa Ken Yoshikawa Kazutoyo Sato Masami Narita Shuichi Ohuchida Hisao Nakai Masaaki Toda 《Bioorganic & medicinal chemistry letters》2010,20(8):2639-2643
A series of novel N-acylsulfonamide analogs were synthesized and evaluated for their binding affinity and antagonist activity for the EP3 receptor subtype. Representative compounds were also evaluated for their inhibitory effect on PGE2-induced uterine contraction in pregnant rats. Among those tested, a series of N-acylbenzenesulfonamide analogs were found to be more potent than the corresponding carboxylic acid analogs in both the in vitro and in vivo evaluations. The structure activity relationships (SAR) are also discussed. 相似文献