全文获取类型
收费全文 | 2244篇 |
免费 | 128篇 |
国内免费 | 2篇 |
专业分类
2374篇 |
出版年
2023年 | 3篇 |
2022年 | 15篇 |
2021年 | 28篇 |
2020年 | 11篇 |
2019年 | 20篇 |
2018年 | 55篇 |
2017年 | 23篇 |
2016年 | 37篇 |
2015年 | 68篇 |
2014年 | 85篇 |
2013年 | 140篇 |
2012年 | 156篇 |
2011年 | 139篇 |
2010年 | 115篇 |
2009年 | 104篇 |
2008年 | 139篇 |
2007年 | 171篇 |
2006年 | 160篇 |
2005年 | 134篇 |
2004年 | 139篇 |
2003年 | 121篇 |
2002年 | 153篇 |
2001年 | 22篇 |
2000年 | 18篇 |
1999年 | 28篇 |
1998年 | 37篇 |
1997年 | 27篇 |
1996年 | 24篇 |
1995年 | 14篇 |
1994年 | 18篇 |
1993年 | 19篇 |
1992年 | 14篇 |
1991年 | 5篇 |
1990年 | 8篇 |
1989年 | 13篇 |
1988年 | 10篇 |
1987年 | 9篇 |
1986年 | 5篇 |
1985年 | 10篇 |
1984年 | 11篇 |
1983年 | 4篇 |
1982年 | 12篇 |
1981年 | 7篇 |
1980年 | 5篇 |
1979年 | 7篇 |
1978年 | 6篇 |
1975年 | 5篇 |
1971年 | 3篇 |
1966年 | 2篇 |
1963年 | 2篇 |
排序方式: 共有2374条查询结果,搜索用时 15 毫秒
31.
Osamu Takase Masahiro Yoshikawa Mana Idei Junichi Hirahashi Toshiro Fujita Tsuyoshi Takato Takayuki Isagawa Genta Nagae Hirofumi Suemori Hiroyuki Aburatani Keiichi Hishikawa 《PloS one》2013,8(2)
NF-κB signaling plays an essential role in maintaining the undifferentiated state of embryonic stem (ES) cells. However, opposing roles of NF-κB have been reported in mouse and human ES cells, and the role of NF-κB in human induced pluripotent stem (iPS) cells has not yet been clarified. Here, we report the role of NF-κB signaling in maintaining the undifferentiated state of human iPS cells. Compared with differentiated cells, undifferentiated human iPS cells showed an augmentation of NF-κB activity. During differentiation induced by the removal of feeder cells and FGF2, we observed a reduction in NF-κB activity, the expression of the undifferentiation markers Oct3/4 and Nanog, and the up-regulation of the differentiated markers WT-1 and Pax-2. The specific knockdown of NF-κB signaling using p65 siRNA also reduced the expression of Oct3/4 and Nanog and up-regulated WT-1 and Pax-2 but did not change the ES-like colony formation. Our results show that the augmentation of NF-κB signaling maintains the undifferentiated state of human iPS and suggest the importance of this signaling pathway in maintenance of human iPS cells. 相似文献
32.
Hirotaka Furukawa Marco Wieser Hiroshi Morita Tsuyoshi Sugio T. Nagasawa 《Archives of microbiology》1998,171(1):37-43
Pseudomonas fluorescens E118 was isolated from soil as an effective eugenol-degrading organism by a screening using eugenol as enrichment substrate.
The first enzyme involved in the degradation of eugenol in this organism, eugenol dehydrogenase, was purified after induction
by eugenol, and the purity of the enzyme was shown by SDS-PAGE and gel-permeation HLPC. The enzyme is a heterodimer that consists
of a 10-kDa cytochrome c and a 58-kDa subunit. The larger subunit presumably contains flavin, suggesting a flavocytochrome c structure and an electron transfer via flavin and cytochrome c during dehydrogenation. The activity of the purified enzyme depended on the addition of a final electron acceptor such as
phenazine methosulfate, 2,6-dichlorophenol-indophenol, cytochrome c, or potassium ferricyanide. The enzyme catalyzed the dehydrogenation of three different 4-hydroxybenzylic structures including
the conversion of eugenol to coniferyl alcohol, 4-alkylphenols to 1-(4-hydroxyphenyl)alcohols, and 4-hydroxybenzylalcohols
to the corresponding aldehydes. The catalytic and structural similarity between this enzyme and a Penicillium vanillyl-alcohol oxidase and 4-alkylphenol methylhydroxylases from several Pseudomonas species is discussed.
Received: 17 June 1998 / Accepted: 12 October 1998 相似文献
33.
Junko Tokuno Tsuyoshi Shoji Ryota Sumitomo Yuichiro Ueda Keiji Yamanashi Cheng-long Huang 《World journal of surgical oncology》2017,15(1):212
Background
Video-assisted thoracic surgery (VATS) plays an important role in thoracic surgery because it is less invasive. However, the existence of severe pleural adhesions may make VATS difficult and complicated. The aim of this study was to assess the utility of inspiration and expiration computed tomography (respiratory dynamic CT (RD-CT)) in evaluation of pleural adhesions preoperatively.Methods
RD-CT was performed on 107 patients undergoing thoracotomies (both VATS and open). We assessed synchronous motion during respiration on RD-CT. Comparing the results of RD-CT and intraoperative findings, we assessed the utility of preoperative evaluation.Results
A negative correlation between sliding score and adhesion grade was revealed. Sliding score in adhesion negative patients was significantly higher than that in adhesion positive patients (P?<?0.0001). The sensitivity of RD-CT was 63.6%, specificity was 74.1%, and accuracy was 72%. Among 62 patients with a CT-Respiration Ratio of less than 0.65, the sensitivity of RD-CT was 77.8%, specificity was 86.8%, and accuracy was 85.5%.Conclusions
RD-CT may be clinically useful for detecting the presence of pleural adhesions. It can be adopted as one of the criteria for deciding the surgical approach.34.
Biserka Mulac-Jericevic Taghi Manshouri Tsuyoshi Yokoi M. Zouhair Atassi 《The protein journal》1988,7(2):173-177
A set of 18 synthetic uniform overlapping peptides spanning the entire extracellular part (residues 1–210) of the α-subunit of human acetylcholine receptor were studied for their binding activity of125I-labeled α-bungarotoxin and cobratoxin. A major toxin-binding region was found to reside within peptide α122–138. In addition, low-binding activities were obtained with peptides α34–49 and α194–210. It is concluded that the region within residues α122–138 constitutes a universal major toxin-binding region for acetylcholine receptor of various species. 相似文献
35.
Tsuyoshi Watabe Kentaro Watanabe Hiroaki Nakano Hiroaki Kato Eiichi Kodama Kazuo Kitaura Nobutaka Fujii 《Journal of molecular biology》2009,392(3):657-39480
The S138A substitution of fusion inhibitory peptides derived from the C-terminal heptad repeat (C-HR) of the human immunodeficiency virus type 1 (HIV-1) gp41 leads to enhanced binding affinity to the N-terminal heptad repeat (N-HR). As such, these peptides exhibit highly potent anti-HIV-1 activity. X-ray crystallographic analysis was performed to understand the effect of the substitution on binding affinity. The comparison of the native and S138A crystal structures indicated that the increase in the hydrophobicity of the S138A substitution may aid the stabilization of the N-HR/C-HR complex through additional hydrophobic contacts. Free-energy calculations suggest that the difference between the desolvation free energies of the C-HR-derived peptides with and without the S138A mutation dominates the observed difference in anti-HIV-1 activity. 相似文献
36.
Hiroshi Gomi Satomi Morikawa Naoki Shinmura Hiroaki Moki Tadashi Yasui Azuma Tsukise Seiji Torii Tsuyoshi Watanabe Yoshinori Maeda Masahiro Hosaka 《The journal of histochemistry and cytochemistry》2015,63(5):350-366
The expression of secretogranin III (SgIII) in chicken endocrine cells has not been investigated. There is limited data available for the immunohistochemical localization of SgIII in the brain, pituitary, and pancreatic islets of humans and rodents. In the present study, we used immunoblotting to reveal the similarities between the expression patterns of SgIII in the common endocrine glands of chickens and rats. The protein–protein interactions between SgIII and chromogranin A (CgA) mediate the sorting of CgA/prohormone core aggregates to the secretory granule membrane. We examined these interactions using co-immunoprecipitation in chicken endocrine tissues. Using immunohistochemistry, we also examined the expression of SgIII in a wide range of chicken endocrine glands and gastrointestinal endocrine cells (GECs). SgIII was expressed in the pituitary, pineal, adrenal (medullary parts), parathyroid, and ultimobranchial glands, but not in the thyroid gland. It was also expressed in GECs of the stomach (proventriculus and gizzard), small and large intestines, and pancreatic islet cells. These SgIII-expressing cells co-expressed serotonin, somatostatin, gastric inhibitory polypeptide, glucagon-like peptide-1, glucagon, or insulin. These results suggest that SgIII is expressed in the endocrine cells that secrete peptide hormones, which mature via the intragranular enzymatic processing of prohormones and physiologically active amines in chickens. 相似文献
37.
Taketo Uchiyama Norifumi Tatsumi Sahoko Kamejima Tsuyoshi Waku Ichiro Ohkido Keitaro Yokoyama Takashi Yokoo Masataka Okabe 《Human cell》2016,29(4):155-161
Chronic kidney disease (CKD) disrupts mineral homeostasis and its representative pathosis is defined as secondary hyperparathyroidism (SHPT). SHPT occurs during the early course of progressive renal insufficiency, and is associated with mortality and cardiovascular events. SHPT results in reduction of calcium-sensing receptor (CaSR) and vitamin D receptor (VDR) in the parathyroid glands during CKD. However, the precise mechanism of CaSR and VDR reduction is largely unknown. CKD was induced through two-step 5/6 nephrectomy, and then CKD rats and sham-operated rats were maintained for 8 weeks on diets containing 0.7 % phosphorus (normal phosphate) or 1.2 % phosphorus (high phosphate). In gene expression analysis, TaqMan probes were used for quantitative real-time polymerase chain reaction. Finally, CaSR and VDR protein expressions were analyzed using immunohistochemistry. DNA methylation analysis was performed using a restriction digestion and quantitative PCR. CaSR and VDR mRNA were reduced only in CKD rats fed the high-phosphorus diets (CKD HP), then CaSR and VDR immunohistochemical expressions were compatible with gene expression assay. SHPT was then confirmed only in CKD HP rats. Furthermore, sole CKD HP rats showed the hypermethylation in CaSR and VDR genes; however, the percentage methylation of both genes was low. Although CaSR and VDR hypermethylation was demonstrated in PTGs of CKD HP rats, the extent of hypermethylation was insufficient to support the relevance between hypermethylation and down-regulation of gene expression because of the low percentage of methylation. Consequently, our data suggest that mechanisms, other than DNA hypermethylation, were responsible for the reduction in mRNA and protein levels of CaSR and VDR in PTGs of CKD HP rats. 相似文献
38.
A group of Fusarium isolates from slime flux similar to F. aquaeductuum produced unique, strongly curved, aseptate, C-shaped conidia. They were found to be identical to F. splendens nom. nud. Dried specimens from which F. splendens was originally isolated were reexamined and characterized as a new species of Cosmospora. Cosmospora matuoi sp. nov. is proposed for the teleomorph, and Fusarium matuoi sp. nov. is proposed for its anamorph. 相似文献
39.
Butterfly wing color-patterns are determined in the prospective wing tissues during the late larval and early pupal stages. To study the cellular differentiation process of wings, morphological knowledge on pupal wings is prerequisite. Here we systematically examined morphological patterns of the pupal wing cuticular surface in a wide variety of nymphalid butterflies in relation to adult color-patterns. Several kinds of pupal wing patterns corresponding to particular adult color-pattern elements were widely observed in many species. Especially noteworthy were the pupal "focal" spots corresponding to the adult border ocelli system, which were detected in many species of Nymphalinae, Apaturinae, Argynninae, Satyrinae, and Danainae. Striped patterns on the pupal wing cuticle seen in some species of Limenitinae, Ariadnae, and Marpesiinae directly corresponded to those of the adult wings. In Vanessa cardui, eyespot-like pattern elements were tentatively produced during development in the wing tissue underneath the pupal spots and subsequently erased, suggesting a mechanism for producing novel color-patterns in the course of development and evolution. The pupal focal spots reasonably correlated with the adult eyespots in size in Precis orithya and Ypthima argus. We physically damaged the pupal focal spots and their corresponding cells underneath in these species, which abolished or inhibited the formation of the adult eyespots. Taken together, our results clarified that pupal cuticle patterns were often indicative of the adult color-patterns and apparently reflect molecular activity of organizing centers for the adult color-pattern formation at least in nymphalid butterflies. 相似文献
40.