全文获取类型
收费全文 | 1616篇 |
免费 | 84篇 |
专业分类
1700篇 |
出版年
2022年 | 9篇 |
2021年 | 23篇 |
2020年 | 9篇 |
2019年 | 11篇 |
2018年 | 24篇 |
2017年 | 17篇 |
2016年 | 30篇 |
2015年 | 39篇 |
2014年 | 56篇 |
2013年 | 82篇 |
2012年 | 108篇 |
2011年 | 105篇 |
2010年 | 65篇 |
2009年 | 59篇 |
2008年 | 98篇 |
2007年 | 105篇 |
2006年 | 102篇 |
2005年 | 106篇 |
2004年 | 99篇 |
2003年 | 103篇 |
2002年 | 87篇 |
2001年 | 32篇 |
2000年 | 25篇 |
1999年 | 30篇 |
1998年 | 21篇 |
1997年 | 13篇 |
1996年 | 14篇 |
1995年 | 15篇 |
1994年 | 10篇 |
1993年 | 17篇 |
1992年 | 17篇 |
1991年 | 22篇 |
1990年 | 11篇 |
1989年 | 8篇 |
1988年 | 15篇 |
1987年 | 10篇 |
1986年 | 11篇 |
1985年 | 17篇 |
1984年 | 17篇 |
1983年 | 8篇 |
1982年 | 14篇 |
1981年 | 12篇 |
1979年 | 8篇 |
1978年 | 4篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1973年 | 1篇 |
1971年 | 2篇 |
1969年 | 1篇 |
排序方式: 共有1700条查询结果,搜索用时 15 毫秒
971.
In order to elucidate the nature of malodor from piggery wastes, volatile compounds in fresh faeces, fresh urine, rotten urine, and rotten mixtures of faeces and urine were isolated by freeze vacuum distillation and continuous extraction and identified by gas chromatography-mass spectrometry. Many alcohols were detected not in fresh urine, but in faeces. Various fatty acids were determined at high concentrations in all samples, but their abundance was different in faeces and urine. Large amounts of phenols came from urine. Aromatic carboxylic acids were detected only in urine and decreased rapidly during digestion. Indole and 3-methylindole which were present only in faeces showed a reverse change of concentration during digestion. 相似文献
972.
R. D. Storer J. E. French L. A. Donehower D. Gulezian K. Mitsumori L. Recio R. H. Schiestl F. D. Sistare N. Tamaoki T. Usui H. van Steeg IWGT Working Group 《Mutation Research - Genetic Toxicology and Environmental Mutagenesis》2003,540(2):165
Genetically altered mouse models (GAMM) for human cancers have been critical to the investigation and characterization of oncogene and tumor suppressor gene expression and function and the associated cancer phenotype. Similarly, several of the mouse models with defined genetic alterations have shown promise for identification of potential human carcinogens and investigation of mechanisms of carcinogen–gene interactions and tumorigenesis. In particular, both the B6.129N5-Trp53 mouse, heterozygous for a p53 null allele, and the CB6F1-RasH2 mouse, hemizygous for the human H-ras transgene, have been extensively investigated. Using 26-week exposure protocols at or approaching the maximum tolerated dose, the summary results to date indicate the potential for GAMM to identify and, possibly, classify chemicals of potential risk to humans using short-term carcinogenicity experiments. This IWGT session focused on: (1) the development of recommendations for genetic/molecular characterization required in animals, tissues, and tumors before and after treatment for identification of presumptive human carcinogens based on the current state of knowledge, (2) identification of data gaps in our current state of knowledge, and (3) development of recommendations for research strategies for further development of our knowledge base of these particular models. By optimization of protocols and identification of significant outcomes and responses to chemical exposure in appropriate short-term mechanism-based genetically altered rodent models, strategies for prevention and intervention may be developed and employed to the benefit of public health. 相似文献
973.
Photoinduced H2 production with Mg chlorophyll-a from Spirulina as a visible light photosensitizer by use of a three component system consisting of NADPH as an electron donor, Methyl Viologen as electron relay and colloidal platinum as catalyst was investigated. By using this system, the H2 production rate was estimated to be 0.70 ± 0.03 × 10–6 mol h–1. 相似文献
974.
Ichiro Hayakawa Akiyuki Ikedo Takumi Chinen Takeo Usui Hideo Kigoshi 《Bioorganic & medicinal chemistry》2012,20(19):5745-5756
Various analogues of glaziovianin A, an antitumor isoflavone, were synthesized, and their biological activities were evaluated. O7-modified glaziovianin A showed strong cytotoxicity against HeLa S3 cells. Compared to glaziovianin A, the O7-benzyl and O7-propargyl analogues were more cytotoxic against HeLa S3 cells and more potent M-phase inhibitors. Furthermore, O7-modified molecular probes of glaziovianin A were synthesized for biological studies. 相似文献
975.
T Miyauchi M Ariki H Usui K Semba Y Matsuzawa T Yamamoto K Toyoshima M Takeda 《Journal of biochemistry》1992,112(6):729-732
Four tyrosine-protein kinases that reacted with antibodies specific to p62c-yes, p60c-src, p60c-src+, and p59fyn, respectively, were solubilized from a rat brain particulate fraction and separated by casein-Toyopearl column chromatography. Possible p59fyn, with a pI of 6.5, was purified 490-fold as a single 59-kDa protein band on SDS-PAGE. The purified enzyme contained almost no phosphotyrosine residues but was autophosphorylated with Mg2+. ATP exclusively at tyrosine residues, with a concomitant increase in the kinase activity toward tyrosine-glutamate (1:4) copolymers. The rate of the copolymer phosphorylation was proportional to the square of the enzyme concentration, suggesting activation through intermolecular catalysis. In the presence of Mn2+, however, the reaction showed a first-order dependence on the enzyme concentration. 相似文献
976.
Chin Wee Tan Yumiko Hirokawa Bruce S. Gardiner David W. Smith Antony W. Burgess 《PloS one》2013,8(10)
The process of crypt formation and the roles of Wnt and cell-cell adhesion signaling in cryptogenesis are not well described; but are important to the understanding of both normal and cancer colon crypt biology. A quantitative 3D-microscopy and image analysis technique is used to study the frequency, morphology and molecular topography associated with crypt formation. Measurements along the colon reveal the details of crypt formation and some key underlying biochemical signals regulating normal colon biology. Our measurements revealed an asymmetrical crypt budding process, contrary to the previously reported symmetrical fission of crypts. 3D immunofluorescence analyses reveals heterogeneity in the subcellular distribution of E-cadherin and β-catenin in distinct crypt populations. This heterogeneity was also found in asymmetrical budding crypts. Singular crypt formation (i.e. no multiple new crypts forming from one parent crypt) were observed in crypts isolated from the normal colon mucosa, suggestive of a singular constraint mechanism to prevent aberrant crypt production. The technique presented improves our understanding of cryptogenesis and suggests that excess colon crypt formation occurs when Wnt signaling is perturbed (e.g. by truncation of adenomatous polyposis coli, APC protein) in most colon cancers. 相似文献
977.
Some of extracellular serine proteases with trypsin-like specificity of cleavage have been known to increase the release of
inflammatory mediators from various cell types. For instance, two well-known trypsin-like serine proteases circulating in
blood, granzyme A (GrA) and thrombin, have been found to promote interleukin (IL)-8 release from an alveolar epithelial A549
cell line. However, the mechanisms by which the proteases promote IL-8 release from the cells are not fully understood. In
the present study, using A549 cells we found that (1) thrombin promoted IL-8 release from the cells via a mechanism partially
involving activation of protease-activated receptor-1, a G-protein coupled receptor, whereas a recombinant form of GrA (rGrA)
did it via a mechanism that does not involve the receptor activation; that (2) unlike rGrA, thrombin did not cause detachment
and microtubule disruption of the cells; and that (3) the release of IL-8 induced by rGrA was inhibited in the presence of
taxol, a microtubule-stabilizing reagent, whereas that induced by thrombin was not. These findings suggest that rGrA and thrombin
promote the release of IL-8 from A549 cells through distinct mechanisms. 相似文献
978.
Yuko Ishikawa Hiroko Ida-Yonemochi Hironobu Suzuki Kuniko Nakakura-Ohshima Han-Sung Jung Masaki J. Honda Yumiko Ishii Nobukazu Watanabe Hayato Ohshima 《Histochemistry and cell biology》2010,134(3):227-241
Recent studies have demonstrated that human dental pulp contains adult stem cells. A pulse of the thymidine analog BrdU given
to young animals at the optimal time could clarify where slow-cycling long-term label-retaining cells (LRCs), putative adult
stem cells, reside in the pulp tissue. This study focuses on the mapping of LRCs in growing teeth and their regenerative capacity
after tooth injuries. Two to seven peritoneal injections of BrdU into pregnant Wistar rats revealed slow-cycling long-term
dense LRCs in the mature tissues of born animals. Numerous dense LRCs were postnatally decreased in number and reached a plateau
at 4 weeks after birth when they mainly resided in the center of the dental pulp, associating with blood vessels. Mature dental
pulp cells were stained with Hoechst 33342 and sorted into (<0.76%) side population cells using FACS, which included dense
LRCs. Some dense LRCs co-expressed mesenchymal stem cell markers such as STRO-1 or CD146. Tooth injuries caused degeneration
of the odontoblast layer, and newly differentiated odontoblast-like cells contained LRCs. Thus, dense LRCs in mature pulp
tissues were supposed to be dental pulp stem cells possessing regenerative capacity for forming newly differentiated odontoblast-like
cells. The present study proposes the new hypothesis that both granular and dense LRCs are equipped in the dental pulp and
that the dense LRCs with proliferative capacity play crucial roles in the pulpal healing process following exogenous stimuli
in cooperation with the granular LRCs. 相似文献
979.
Hideaki Fujii Yoshihiro Ida Shinichi Hanamura Yumiko Osa Toru Nemoto Mayumi Nakajima Ko Hasebe Kaoru Nakao Hidenori Mochizuki Hiroshi Nagase 《Bioorganic & medicinal chemistry letters》2010,20(17):5035-5038
We synthesized pyrrolomorphinan derivatives 6, 7, and 9 to examine whether the pyrrole ring would be an accessory site in the κ opioid receptor selective antagonist, nor-binaltorphimine. Derivative 6 had an α,β-unsaturated ketone substituent that strongly bound to the κ receptor. The compound with the highest κ receptor selectivity, 6e, produced a dose-dependent antinociceptive effect in the mouse acetic acid writhing test. However, derivatives 7 and 9, which did not have α,β-unsaturated ketone substituents, showed less κ receptor selectivity than compound 6. Based on structure–activity relationships, we proposed that these compounds adopted active structures for κ selective agonist activity. The pyrrole ring would not function as an accessory site, but the ability of the side chain on the pyrrole ring to localize above the C-ring appeared to confer κ selective agonist activity. These results will promote the design of novel κ agonists. 相似文献
980.
Ryoichi Ando Hiroshi Ikegami Makoto Sakiyama Shinsuke Ooike Masayuki Hayashi Yasuhiro Fujino Daisuke Abe Hideo Nakamura Tadashi Mishina Harutoshi Kato Yumiko Iwase Hideo Tomozane Masahiko Morioka 《Bioorganic & medicinal chemistry letters》2010,20(15):4709-4711
A new class of Aurora A kinase inhibitor was created by transforming 4-(5-methyl-3-pyrazoloamino)pyrimidine moiety of VX-680 to 3-cyano-6-(5-methyl-3pyrazoloamino)pyridine. Compound 6 exhibited a potent Aurora A kinase inhibitory activity, excellent selectivity to Aurora B kinase and other 60 kinases, good cell permeability and good PK profile. Therefore compound 6 was effective in antitumor mice model at a dose of 30 mg/kg po qd without decrease of body weight. 相似文献