全文获取类型
收费全文 | 2381篇 |
免费 | 120篇 |
出版年
2022年 | 9篇 |
2021年 | 24篇 |
2020年 | 20篇 |
2019年 | 16篇 |
2018年 | 28篇 |
2017年 | 28篇 |
2016年 | 38篇 |
2015年 | 55篇 |
2014年 | 89篇 |
2013年 | 143篇 |
2012年 | 131篇 |
2011年 | 125篇 |
2010年 | 79篇 |
2009年 | 86篇 |
2008年 | 121篇 |
2007年 | 128篇 |
2006年 | 123篇 |
2005年 | 120篇 |
2004年 | 130篇 |
2003年 | 145篇 |
2002年 | 131篇 |
2001年 | 49篇 |
2000年 | 57篇 |
1999年 | 53篇 |
1998年 | 18篇 |
1997年 | 28篇 |
1996年 | 19篇 |
1995年 | 30篇 |
1994年 | 34篇 |
1993年 | 22篇 |
1992年 | 23篇 |
1991年 | 22篇 |
1990年 | 28篇 |
1989年 | 31篇 |
1988年 | 33篇 |
1987年 | 31篇 |
1986年 | 16篇 |
1985年 | 33篇 |
1984年 | 22篇 |
1983年 | 18篇 |
1982年 | 19篇 |
1980年 | 14篇 |
1979年 | 27篇 |
1978年 | 19篇 |
1977年 | 7篇 |
1976年 | 10篇 |
1975年 | 9篇 |
1974年 | 8篇 |
1973年 | 8篇 |
1968年 | 8篇 |
排序方式: 共有2501条查询结果,搜索用时 31 毫秒
21.
Martins Renato Tavares de Freitas Silva Rafael Augusto Pinheiro Pinto Valria Arajo Braule Medeiros Adriana Oliveira Brito Laisa Hamada Neusa 《Hydrobiologia》2022,849(16):3531-3544
Hydrobiologia - We used experimental chambers to evaluate the effect of the temperature increasing and microbial conditioning degree on the survival and leaf consumption of two plant species... 相似文献
22.
Hikaru Tsukazaki Shigenori Yaguchi Shusei Sato Hideki Hirakawa Yuichi Katayose Hiroyuki Kanamori Kanako Kurita Takeshi Itoh Masahiko Kumagai Satoshi Mizuno Masao Hamada Hiroyuki Fukuoka Ken-ichiro Yamashita John A. McCallum Masayoshi Shigyo Tadayuki Wako 《Molecular breeding : new strategies in plant improvement》2015,35(1):1-11
23.
Hiroyuki Hirakawa Hirofumi Zempo Masahito Ogawa Ryo Watanabe Jun-ichi Suzuki Hiroshi Akazawa Issei Komuro Mitsuaki Isobe 《PloS one》2015,10(3)
Myocarditis is a critical inflammatory disorder which causes life-threatening conditions. No specific or effective treatment has been established. DPP-4 inhibitors have salutary effects not only on type 2 diabetes but also on certain cardiovascular diseases. However, the role of a DPP-4 inhibitor on myocarditis has not been investigated. To clarify the effects of a DPP-4 inhibitor on myocarditis, we used an experimental autoimmune myocarditis (EAM) model in Balb/c mice. EAM mice were assigned to the following groups: EAM mice group treated with a DPP-4 inhibitor (linagliptin) (n = 19) and those untreated (n = 22). Pathological analysis revealed that the myocardial fibrosis area ratio in the treated group was significantly lower than in the untreated group. RT-PCR analysis demonstrated that the levels of mRNA expression of IL-2, TNF-α, IL-1β and IL-6 were significantly lower in the treated group than in the untreated group. Lymphocyte proliferation assay showed that treatment with the DPP-4 inhibitor had no effect on antigen-induced spleen cell proliferation. Administration of the DPP-4 inhibitor remarkably suppressed cardiac fibrosis and reduced inflammatory cytokine gene expression in EAM mice. Thus, the agents present in DPP-4 inhibitors may be useful to treat and/or prevent clinical myocarditis. 相似文献
24.
The centrosome-associated C1orf96/Centriole, Cilia and Spindle-Associated Protein (CSAP) targets polyglutamylated tubulin in mitotic microtubules (MTs). Loss of CSAP causes critical defects in brain development; however, it is unclear how CSAP association with MTs affects mitosis progression. In this study, we explored the molecular mechanisms of the interaction of CSAP with mitotic spindles. Loss of CSAP caused MT instability in mitotic spindles and resulted in mislocalization of Nuclear protein that associates with the Mitotic Apparatus (NuMA), with defective MT dynamics. Thus, CSAP overload in the spindles caused extensive MT stabilization and recruitment of NuMA. Moreover, MT stabilization by CSAP led to high levels of polyglutamylation on MTs. MT depolymerization by cold or nocodazole treatment was inhibited by CSAP binding. Live-cell imaging analysis suggested that CSAP-dependent MT-stabilization led to centrosome-free MT aster formation immediately upon nuclear envelope breakdown without γ-tubulin. We therefore propose that CSAP associates with MTs around centrosomes to stabilize MTs during mitosis, ensuring proper bipolar spindle formation and maintenance. 相似文献
25.
Norishige Yamada Yuko Hasegawa Minghui Yue Tomofumi Hamada Shinichi Nakagawa Yuya Ogawa 《PLoS genetics》2015,11(8)
To equalize X-linked gene dosage between the sexes in mammalian females, Xist RNA inactivates one of the two X-chromosomes. Here, we report the crucial function of Xist exon 7 in X-inactivation. Xist exon 7 is the second-largest exon with a well-conserved repeat E in eutherian mammals, but its role is often overlooked in X-inactivation. Although female ES cells with a targeted truncation of the Xist exon 7 showed no significant differences in their Xist expression levels and RNA stability from control cells expressing wild-type Xist, compromised localization of Xist RNA and incomplete silencing of X-linked genes on the inactive X-chromosome (Xi) were observed in the exon 7-truncated mutant cells. Furthermore, the interaction between the mutant Xist RNA and hnRNP U required for localization of Xist RNA to the Xi was impaired in the Xist exon 7 truncation mutant cells. Our results suggest that exon 7 of Xist RNA plays an important role for stable Xist RNA localization and silencing of the X-linked genes on the Xi, possibly acting through an interaction with hnRNP U. 相似文献
26.
Shusuke Numata Kazuo Ishii Atsushi Tajima Jun-ichi Iga Makoto Kinoshita Shinya Watanabe Hidehiro Umehara Manabu Fuchikami Satoshi Okada Shuken Boku Akitoyo Hishimoto Shinji Shimodera Issei Imoto Shigeru Morinobu Tetsuro Ohmori 《Epigenetics》2015,10(2):135-141
Aberrant DNA methylation in the blood of patients with major depressive disorder (MDD) has been reported in several previous studies. However, no comprehensive studies using medication-free subjects with MDD have been conducted. Furthermore, the majority of these previous studies has been limited to the analysis of the CpG sites in CpG islands (CGIs) in the gene promoter regions. The main aim of the present study is to identify DNA methylation markers that distinguish patients with MDD from non-psychiatric controls. Genome-wide DNA methylation profiling of peripheral leukocytes was conducted in two set of samples, a discovery set (20 medication-free patients with MDD and 19 controls) and a replication set (12 medication-free patients with MDD and 12 controls), using Infinium HumanMethylation450 BeadChips. Significant diagnostic differences in DNA methylation were observed at 363 CpG sites in the discovery set. All of these loci demonstrated lower DNA methylation in patients with MDD than in the controls, and most of them (85.7%) were located in the CGIs in the gene promoter regions. We were able to distinguish patients with MDD from the control subjects with high accuracy in the discriminant analysis using the top DNA methylation markers. We also validated these selected DNA methylation markers in the replication set. Our results indicate that multiplex DNA methylation markers may be useful for distinguishing patients with MDD from non-psychiatric controls. 相似文献
27.
28.
Amit Kumar Sinha Hamada AbdElgawad Gaurav Zinta Antony Franklin Dasan Rindra Rasoloniriana Han Asard Ronny Blust Gudrun De Boeck 《PloS one》2015,10(8)
Salinity fluctuation is one of the main factors affecting the overall fitness of marine fish. In addition, water borne ammonia may occur simultaneously with salinity stress. Additionally, under such stressful circumstances, fish may encounter food deprivation. The physiological and ion-osmo regulatory adaptive capacities to cope with all these stressors alone or in combination are extensively addressed in fish. To date, studies revealing the modulation of antioxidant potential as compensatory response to multiple stressors are rather lacking. Therefore, the present work evaluated the individual and combined effects of salinity challenge, ammonia toxicity and nutritional status on oxidative stress and antioxidant status in a marine teleost, European sea bass (Dicentrarchus labrax). Fish were acclimated to normal seawater (32 ppt), to brackish water (20 ppt and 10 ppt) and to hypo-saline water (2.5 ppt). Following acclimation to different salinities for two weeks, fish were exposed to high environmental ammonia (HEA, 20 mg/L representing 50% of 96h LC50 value for ammonia) for 12 h, 48 h, 84 h and 180 h, and were either fed (2% body weight) or fasted (unfed for 7 days prior to HEA exposure). Results show that in response to decreasing salinities, oxidative stress indices such as xanthine oxidase activity, levels of hydrogen peroxide (H2O2) and lipid peroxidation (malondialdehyde, MDA) increased in the hepatic tissue of fasted fish but remained unaffected in fed fish. HEA exposure at normal salinity (32 ppt) and at reduced salinities (20 ppt and 10 ppt) increased ammonia accumulation significantly (84 h–180 h) in both feeding regimes which was associated with an increment of H2O2 and MDA contents. Unlike in fasted fish, H2O2 and MDA levels in fed fish were restored to control levels (84 h–180 h); with a concomitant increase in superoxide dismutase (SOD), catalase (CAT), components of the glutathione redox cycle (reduced glutathione, glutathione peroxidase and glutathione reductase), ascorbate peroxidase (APX) activity and reduced ascorbate (ASC) content. On the contrary, fasted fish could not activate many of these protective systems and rely mainly on CAT and ASC dependent pathways as antioxidative sentinels. The present findings exemplify that in fed fish single factors and a combination of HEA exposure and reduced seawater salinities (upto 10 ppt) were insufficient to cause oxidative damage due to the highly competent antioxidant system compared to fasted fish. However, the impact of HEA exposure at a hypo-saline environment (2.5 ppt) also defied antioxidant defence system in fed fish, suggesting this combined factor is beyond the tolerance range for both feeding groups. Overall, our results indicate that the oxidative stress mediated by the experimental conditions were exacerbated during starvation, and also suggest that feed deprivation particularly at reduced seawater salinities can instigate fish more susceptible to ammonia toxicity. 相似文献
29.
30.
The Extracellular A-loop of Dual Oxidases Affects the Specificity of Reactive Oxygen Species Release
Takehiko Ueyama Megumi Sakuma Yuzuru Ninoyu Takeshi Hamada Corinne Dupuy Miklós Geiszt Thomas L. Leto Naoaki Saito 《The Journal of biological chemistry》2015,290(10):6495-6506
NADPH oxidase (Nox) family proteins produce superoxide (O2⨪) directly by transferring an electron to molecular oxygen. Dual oxidases (Duoxes) also produce an O2⨪ intermediate, although the final species secreted by mature Duoxes is H2O2, suggesting that intramolecular O2⨪ dismutation or other mechanisms contribute to H2O2 release. We explored the structural determinants affecting reactive oxygen species formation by Duox enzymes. Duox2 showed O2⨪ leakage when mismatched with Duox activator 1 (DuoxA1). Duox2 released O2⨪ even in correctly matched combinations, including Duox2 + DuoxA2 and Duox2 + N-terminally tagged DuoxA2 regardless of the type or number of tags. Conversely, Duox1 did not release O2⨪ in any combination. Chimeric Duox2 possessing the A-loop of Duox1 showed no O2⨪ leakage; chimeric Duox1 possessing the A-loop of Duox2 released O2⨪. Moreover, Duox2 proteins possessing the A-loops of Nox1 or Nox5 co-expressed with DuoxA2 showed enhanced O2⨪ release, and Duox1 proteins possessing the A-loops of Nox1 or Nox5 co-expressed with DuoxA1 acquired O2⨪ leakage. Although we identified Duox1 A-loop residues (His1071, His1072, and Gly1074) important for reducing O2⨪ release, mutations of these residues to those of Duox2 failed to convert Duox1 to an O2⨪-releasing enzyme. Using immunoprecipitation and endoglycosidase H sensitivity assays, we found that the A-loop of Duoxes binds to DuoxA N termini, creating more stable, mature Duox-DuoxA complexes. In conclusion, the A-loops of both Duoxes support H2O2 production through interaction with corresponding activators, but complex formation between the Duox1 A-loop and DuoxA1 results in tighter control of H2O2 release by the enzyme complex. 相似文献