全文获取类型
收费全文 | 1473篇 |
免费 | 81篇 |
专业分类
1554篇 |
出版年
2022年 | 6篇 |
2020年 | 9篇 |
2019年 | 9篇 |
2018年 | 15篇 |
2017年 | 15篇 |
2016年 | 22篇 |
2015年 | 33篇 |
2014年 | 41篇 |
2013年 | 101篇 |
2012年 | 68篇 |
2011年 | 75篇 |
2010年 | 32篇 |
2009年 | 54篇 |
2008年 | 77篇 |
2007年 | 53篇 |
2006年 | 94篇 |
2005年 | 81篇 |
2004年 | 72篇 |
2003年 | 87篇 |
2002年 | 91篇 |
2001年 | 16篇 |
2000年 | 20篇 |
1999年 | 22篇 |
1998年 | 36篇 |
1997年 | 27篇 |
1996年 | 21篇 |
1995年 | 23篇 |
1994年 | 24篇 |
1993年 | 19篇 |
1992年 | 14篇 |
1991年 | 11篇 |
1990年 | 12篇 |
1989年 | 12篇 |
1988年 | 13篇 |
1987年 | 6篇 |
1986年 | 13篇 |
1985年 | 9篇 |
1984年 | 16篇 |
1983年 | 13篇 |
1982年 | 23篇 |
1981年 | 25篇 |
1980年 | 15篇 |
1979年 | 20篇 |
1978年 | 11篇 |
1977年 | 8篇 |
1976年 | 17篇 |
1975年 | 7篇 |
1974年 | 14篇 |
1973年 | 12篇 |
1972年 | 7篇 |
排序方式: 共有1554条查询结果,搜索用时 0 毫秒
61.
In Escherichia coli, chemoreceptor clustering at a cell pole seems critical for signal amplification and adaptation. However, little is known about the mechanism of localization itself. Here we examined whether the aspartate chemoreceptor (Tar) is inserted directly into the polar membrane by using its fusion to green fluorescent protein (GFP). After induction of Tar-GFP, fluorescent spots first appeared in lateral membrane regions, and later cell poles became predominantly fluorescent. Unexpectedly, Tar-GFP showed a helical arrangement in lateral regions, which was more apparent when a Tar-GFP derivative with two cysteine residues in the periplasmic domain was cross-linked to form higher oligomers. Moreover, similar distribution was observed even when the cytoplasmic domain of the double cysteine Tar-GFP mutant was replaced by that of the kinase EnvZ, which does not localize to a pole. Observation of GFP-SecE and a translocation-defective MalE-GFP mutant, as well as indirect immunofluorescence microscopy on SecG, suggested that the general protein translocation machinery (Sec) itself is arranged into a helical array, with which Tar is transiently associated. The Sec coil appeared distinct from the MreB coil, an actin-like cytoskeleton. These findings will shed new light on the mechanisms underlying spatial organization of membrane proteins in E. coli. 相似文献
62.
Sumie S Kawaguchi T Kuromatsu R Takata A Nakano M Satani M Yamada S Niizeki T Torimura T Sata M 《PloS one》2011,6(11):e26840
Background
Adiponectin is shown to be inversely associated with development and progression of various cancers. We evaluated whether adiponectin level was associated with the prevalence and histological grade of hepatocellular carcinoma (HCC), and liver fibrosis in patients with hepatitis C virus (HCV) infection.Methods
A case-control study was conducted on 97 HCC patients (cases) and 97 patients (controls) matched for sex, Child-Pugh grade and platelet count in patients with HCV infection. The serum total and high molecular weight (HMW) adiponectin levels were measured by enzyme-linked immunosorbent assays and examined in their association with the prevalence of HCC. In addition, the relationship between these adiponectin levels and body mass index (BMI), progression of liver fibrosis, and histological grade of HCC was also evaluated. Liver fibrosis was assessed using the aspartate aminotransferase to platelet ratio index (APRI).Results
There were no significant differences in the serum total and HMW adiponectin levels between cases and controls. Moreover, there were no inverse associations between serum total and HMW adiponectin levels and BMI in both cases and controls. On the other hand, serum total and HMW adiponectin levels are positively correlated with APRI in both cases (r = 0.491, P<0.001 and r = 0.485, P<0.001, respectively) and controls (r = 0.482, P<0.001 and r = 0.476, P<0.001, respectively). Interestingly, lower serum total (OR 11.76, 95% CI: 2.97–46.66 [P<0.001]) and HMW (OR 10.24, CI: 2.80–37.40 [P<0.001] adiponectin levels were independent risk factors of worse histological grade of HCC.Conclusions
Our results suggested that serum total and HMW adiponectin levels were predictors of liver fibrosis, but not prevalence of HCC in patients with HCV infection. Moreover, low these adiponectin levels were significantly associated with worse histological grades. 相似文献63.
Using food network unfolding to evaluate food–web complexity in terms of biodiversity: theory and applications 下载免费PDF全文
Yoshikazu Kato Michio Kondoh Naoto F. Ishikawa Hiroyuki Togashi Yukihiro Kohmatsu Mayumi Yoshimura Chikage Yoshimizu Takashi F. Haraguchi Yutaka Osada Nobuhito Ohte Naoko Tokuchi Noboru Okuda Takeshi Miki Ichiro Tayasu 《Ecology letters》2018,21(7):1065-1074
Food–web complexity often hinders disentangling functionally relevant aspects of food–web structure and its relationships to biodiversity. Here, we present a theoretical framework to evaluate food–web complexity in terms of biodiversity. Food network unfolding is a theoretical method to transform a complex food web into a linear food chain based on ecosystem processes. Based on this method, we can define three biodiversity indices, horizontal diversity (DH), vertical diversity (DV) and range diversity (DR), which are associated with the species diversity within each trophic level, diversity of trophic levels, and diversity in resource use, respectively. These indices are related to Shannon's diversity index (H′), where H′ = DH + DV ? DR. Application of the framework to three riverine macroinvertebrate communities revealed that D indices, calculated from biomass and stable isotope features, captured well the anthropogenic, seasonal, or other within‐site changes in food–web structures that could not be captured with H′ alone. 相似文献
64.
Andrew Post T. Blaine Hoshizaki Clara Karton J. Michio Clark Lauren Dawson Janie Cournoyer 《Computer methods in biomechanics and biomedical engineering》2019,22(6):631-643
The purpose of this research was to conduct reconstructions of concussive and non-concussive impacts in ice hockey to determine the biomechanics and thresholds of concussive injury in ice hockey. Videos of concussive and non-concussive impacts in an elite professional ice hockey league in North America were reconstructed using physical and finite element model methods. Eighty concussive and 45 non-concussive events were studied. Logistic regressions indicate significant thresholds for concussion for linear/rotational acceleration and CSDM10%. Impacts in ice hockey were mostly long duration events, longer than 15?ms. These results have significant implications for helmet standards and development to prevent concussion. 相似文献
65.
Toshio Sekiguchi Kenji Kuwasako Michio Ogasawara Hiroki Takahashi Shin Matsubara Tomohiro Osugi Ikunobu Muramatsu Yuichi Sasayama Nobuo Suzuki Honoo Satake 《The Journal of biological chemistry》2016,291(5):2345-2356
The calcitonin (CT)/CT gene-related peptide (CGRP) family is conserved in vertebrates. The activities of this peptide family are regulated by a combination of two receptors, namely the calcitonin receptor (CTR) and the CTR-like receptor (CLR), and three receptor activity-modifying proteins (RAMPs). Furthermore, RAMPs act as escort proteins by translocating CLR to the cell membrane. Recently, CT/CGRP family peptides have been identified or inferred in several invertebrates. However, the molecular characteristics and relevant functions of the CTR/CLR and RAMPs in invertebrates remain unclear. In this study, we identified three CT/CGRP family peptides (Bf-CTFPs), one CTR/CLR-like receptor (Bf-CTFP-R), and three RAMP-like proteins (Bf-RAMP-LPs) in the basal chordate amphioxus (Branchiostoma floridae). The Bf-CTFPs were shown to possess an N-terminal circular region typical of the CT/CGRP family and a C-terminal Pro-NH2. The Bf-CTFP genes were expressed in the central nervous system and in endocrine cells of the midgut, indicating that Bf-CTFPs serve as brain and/or gut peptides. Cell surface expression of the Bf-CTFP-R was enhanced by co-expression with each Bf-RAMP-LP. Furthermore, Bf-CTFPs activated Bf-CTFP-R·Bf-RAMP-LP complexes, resulting in cAMP accumulation. These results confirmed that Bf-RAMP-LPs, like vertebrate RAMPs, are prerequisites for the function and translocation of the Bf-CTFP-R. The relative potencies of the three peptides at each receptor were similar. Bf-CTFP2 was a potent ligand at all receptors in cAMP assays. Bf-RAMP-LP effects on ligand potency order were distinct to vertebrate CGRP/adrenomedullin/amylin receptors. To the best of our knowledge, this is the first molecular and functional characterization of an authentic invertebrate CT/CGRP family receptor and RAMPs. 相似文献
66.
Natural underlying mtDNA heteroplasmy as a potential source of intra‐person hiPSC variability 下载免费PDF全文
Ester Perales‐Clemente Alexandra N Cook Jared M Evans Samantha Roellinger Frank Secreto Valentina Emmanuele Devin Oglesbee Vamsi K Mootha Michio Hirano Eric A Schon Andre Terzic Timothy J Nelson 《The EMBO journal》2016,35(18):1979-1990
Functional variability among human clones of induced pluripotent stem cells (hiPSCs) remains a limitation in assembling high‐quality biorepositories. Beyond inter‐person variability, the root cause of intra‐person variability remains unknown. Mitochondria guide the required transition from oxidative to glycolytic metabolism in nuclear reprogramming. Moreover, mitochondria have their own genome (mitochondrial DNA [mtDNA]). Herein, we performed mtDNA next‐generation sequencing (NGS) on 84 hiPSC clones derived from a cohort of 19 individuals, including mitochondrial and non‐mitochondrial patients. The analysis of mtDNA variants showed that low levels of potentially pathogenic mutations in the original fibroblasts are revealed through nuclear reprogramming, generating mutant hiPSCs with a detrimental effect in their differentiated progeny. Specifically, hiPSC‐derived cardiomyocytes with expanded mtDNA mutations non‐related with any described human disease, showed impaired mitochondrial respiration, being a potential cause of intra‐person hiPSC variability. We propose mtDNA NGS as a new selection criterion to ensure hiPSC quality for drug discovery and regenerative medicine. 相似文献
67.
Osada Kazumi; Komai Michio; Bryant Bruce P.; Suzuki Hitoshi; Goto Atsuko; Tsunoda Kenji; Kimura Shuichi; Furukawa Yuji 《Chemical senses》1997,22(3):249-255
Single-fiber preparations of the rat chorda tympani (CT) nervewere used to study the mechanism of action of capsaicin on salt-tastetransduction. Capsaicin selectively suppressed the responsesto NaCl of the CT nerve fibers (N-fibers) that are sodium-specific(insensitive or poorly sensitive to potassium). Among the morebroadly responsive, cation-sensitive fibers (E-fibers) thereare two subtypes, both of which responded to capsaicin but indifferent ways (enhanced type and suppressedtype). In both N- and E-fibers, 5% ethanol (the vehicle forcapsaicin) slightly reduced the response to 100 mM NaCl. Thesuppressive effect of capsaicin on the response of the N-typefibers to 100 mM NaCl was significantly stronger than the effectof 5% ethanol. The suppression lasted for at least 20 s afterthe simultaneous application of 100 p.p.m. capsaicin-100 mMNaCl. These results indicate that 100 p.p.m. capsaicin can modifythe response of CT fibers to NaCl. The observed effect of capsaicinon gustatory fibers could be the net result of opposite suppressiveand enhancing processes in the taste buds cells and excitedintra- or extragemmal trigeminal nerve endings. Chem. Senses22: 249255, 1997.
*These authors contributed equally to this study 相似文献
68.
Atsushi Hayakawa Kazuo Kuwata Seiichi Era Masaru Sogami Hiroyuki Shimonaka Michio Yamamoto Shuji Dohi Hajime Hirose 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1997,698(1-2)
Human serum albumin is a mixture of mercapt- (HMA, reduced form) and nonmercaptalbumin (HNA, oxidized form). We studied the mercapt↔nonmercapt conversion of human serum albumin, which reflects the redox state of the extracellular fluids, in cardiac and other common surgical patients using high-performance liquid chromatography. Mean values of [(HMA)/(HMA + HNA)] ± standard deviation [fHMA ± σ], for patients who received common surgery (group 1) and cardiac surgery (group 2) at the start of anesthesia were0.636±0.50(n=83) and 0.615±0.062(n=14), respectively. fHMA values were markedly lower than those for healthy male adults of 0.750±0.028(n=28). fHMA values increased at 24 h after the start of anesthesia and decreased on the 4th postoperative day in most of the patients. These postoperative changes were prominent in surgical cardiac patients. Although fHMA values after the 7th postoperative day recovered to those at the start of anesthesia in almost all of common surgical patients, those in cardiac surgical patients, never recovered even on the 21st postoperative day. 相似文献
69.
Identification and Expression of the Genes Encoding a Reactivating Factor for Adenosylcobalamin-Dependent Glycerol Dehydratase 总被引:10,自引:0,他引:10 下载免费PDF全文
Takamasa Tobimatsu Hideki Kajiura Michio Yunoki Muneaki Azuma Tetsuo Toraya 《Journal of bacteriology》1999,181(13):4110-4113
Adenosylcobalamin-dependent glycerol dehydratase undergoes inactivation by glycerol, the physiological substrate, during catalysis. In permeabilized cells of Klebsiella pneumoniae, the inactivated enzyme is reactivated in the presence of ATP, Mg2+, and adenosylcobalamin. We identified the two open reading frames as the genes for a reactivating factor for glycerol dehydratase and designated them gdrA and gdrB. The reactivation of the inactivated glycerol dehydratase by the gene products was confirmed in permeabilized recombinant Escherichia coli cells coexpressing GdrA and GdrB proteins with glycerol dehydratase. 相似文献
70.
Konishi K Watanabe Y Shen L Guo Y Castoro RJ Kondo K Chung W Ahmed S Jelinek J Boumber YA Estecio MR Maegawa S Kondo Y Itoh F Imawari M Hamilton SR Issa JP 《PloS one》2011,6(11):e27889