全文获取类型
收费全文 | 112923篇 |
免费 | 1954篇 |
国内免费 | 2441篇 |
出版年
2024年 | 55篇 |
2023年 | 315篇 |
2022年 | 711篇 |
2021年 | 1152篇 |
2020年 | 766篇 |
2019年 | 977篇 |
2018年 | 12506篇 |
2017年 | 11101篇 |
2016年 | 8240篇 |
2015年 | 1901篇 |
2014年 | 1787篇 |
2013年 | 1857篇 |
2012年 | 6065篇 |
2011年 | 14329篇 |
2010年 | 12870篇 |
2009年 | 9029篇 |
2008年 | 10777篇 |
2007年 | 12161篇 |
2006年 | 1072篇 |
2005年 | 1138篇 |
2004年 | 1460篇 |
2003年 | 1456篇 |
2002年 | 1141篇 |
2001年 | 577篇 |
2000年 | 479篇 |
1999年 | 347篇 |
1998年 | 215篇 |
1997年 | 263篇 |
1996年 | 200篇 |
1995年 | 189篇 |
1994年 | 168篇 |
1993年 | 158篇 |
1992年 | 202篇 |
1991年 | 180篇 |
1990年 | 153篇 |
1989年 | 105篇 |
1988年 | 107篇 |
1987年 | 100篇 |
1986年 | 63篇 |
1985年 | 65篇 |
1984年 | 50篇 |
1983年 | 64篇 |
1982年 | 23篇 |
1981年 | 16篇 |
1980年 | 15篇 |
1972年 | 249篇 |
1971年 | 280篇 |
1965年 | 29篇 |
1962年 | 24篇 |
1944年 | 12篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
941.
Thomas Ross Karol Szczepanek Elizabeth Bowler Ying Hu Andrew Larner Edward J. Lesnefsky Qun Chen 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
The reverse electron flow-induced ROS generation (RFIR) is decreased in ischemia-damaged mitochondria. Cardiac ischemia leads to decreased complex I activity and depolarized inner mitochondrial membrane potential (ΔΨ) that are two key factors to affect the RFIR in isolated mitochondria. We asked if a partial inhibition of complex I activity without alteration of the ΔΨ is able to decrease the RFIR.Methods
Cardiac mitochondria were isolated from mouse heart (C57BL/6) with and without ischemia. The rate of H2O2 production from mitochondria was determined using amplex red coupled with horseradish peroxidase. Mitochondria were isolated from the mitochondrial-targeted STAT3 overexpressing mouse (MLS-STAT3E) to clarify the role of partial complex I inhibition in RFIR production.Results
The RFIR was decreased in ischemia-damaged mouse heart mitochondria with decreased complex I activity and depolarized ΔΨ. However, the RFIR was not altered in the MLS-STAT3E heart mitochondria with complex I defect but without depolarization of the ΔΨ. A slight depolarization of the ΔΨ in wild type mitochondria completely eliminated the RFIR.Conclusions
The mild uncoupling but not the partially decreased complex I activity contributes to the observed decrease in RFIR in ischemia-damaged mitochondria.General significance
The RFIR is less likely to be a key source of cardiac injury during reperfusion. 相似文献942.
Ming Gao Xiaoguang Li Wen Dong Rui Jin Hanghang Ma Pingxun Yang Meiru Hu Yi Li Yi Hao Shengtao Yuan Junjian Huang Lun Song 《Nucleic acids research》2013,41(10):5210-5222
The stress-responding protein, GADD45α, plays important roles in cell cycle checkpoint, DNA repair and apoptosis. In our recent study, we demonstrate that GADD45α undergoes a dynamic ubiquitination and degradation in vivo, which process can be blocked by the cytotoxic reagent, arsenite, resulting in GADD45α accumulation to activate JNKs cell death pathway, thereby revealing a novel mechanism for the cellular GADD45α functional regulation. But the factors involved in GADD45α stability modulations are unidentified. Here, we demonstrated that MDM2 was an E3 ubiquitin ligase for GADD45α. One of MDM2-binding partner, ribosomal protein S7, interacted with and stabilized GADD45α through preventing the ubiquitination and degradation of GADD45α mediated by MDM2. This novel function of S7 is unrelated to p53 but seems to depend on S7/MDM2 interaction, for the S7 mutant lacking MDM2-binding ability lost its function to stabilize GADD45α. Further investigations indicated that arsenite treatment enhanced S7–MDM2 interaction, resulting in attenuation of MDM2-dependent GADD45α ubiquitination and degradation, thereby leading to GADD45α-dependent cell death pathway activation. Silencing S7 expression suppressed GADD45α-dependent cytotoxicity induced by arsenite. Our findings thus identify a novel function of S7 in control of GADD45α stabilization under both basal and stress conditions and its significance in mediating arsenite-induced cellular stress. 相似文献
943.
944.
Yuanqing Hu Yuwei Shang Jinlin Huang Yan Wang Fangzhe Ren Yang Jiao Zhiming Pan Xin-an Jiao 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
Campylobacter jejuni is an important food-borne and zoonotic pathogen with a worldwide distribution. Humans and chickens are hosts of this pathogen. At present, there is no ideal vaccine for controlling human campylobacteriosis or the carriage of C. jejuni by chickens. Bacterial in vivo-induced antigens are useful as potential vaccine candidates and biomarkers of virulence.Methods
In this study, we developed a novel systematic immunoproteomics approach to identify in vivo-induced antigens among the total cell proteins of C. jejuni using pre-adsorbed sera from patients infected with C. jejuni.Results
Overall, 14 immunoreactive spots were probed on a PVDF membrane using pre-adsorbed human sera against C. jejuni. Then, we excised these protein spots from a duplicate gel and identified using MALDI–TOF MS. In total, 14 in vivo-induced antigens were identified using PMF and BLAST analysis. The identified proteins include CadF (CadF-1 and CadF-2), CheW, TufB, DnaK, MetK, LpxB, HslU, DmsA, PorA, ProS, CJBH_0976, CSU_0396 and hypothetical protein cje135_05017. Real-time RT-PCR was performed on 9 genes to compare their expression levels in vivo and in vitro. The data showed that 8 of the 9 analyzed genes were significantly upregulated in vivo relative to in vitro.Conclusion
We successfully developed a novel immunoproteomics method for identifying in vivo-induced Campylobacter jejuni antigens by using pre-adsorbed sera from infected patients.General significance
This new analysis method may prove to be useful for identifying in vivo-induced antigens within any host infected by bacteria and will contribute to the development of new subunit vaccines. 相似文献945.
Yong-Lu Yang Xiao-Song Hu Wang Zan Zi-Ling Sheng Tao Huang Ya-Jun Wei 《Journal of thermal biology》2013
It has been reported that hypothermia induced by arginine vasopressin (AVP) is brought about by a coordinated response of reduced thermogenesis in brown adipose tissue (BAT) and increased heat loss through the tail of rats. However, it is well known that AVP is one of the strongest peripheral vasoconstrictors. Whether the AVP-induced hypothermia is associated with an increase in heat loss through the tail is questionable. Therefore, the present study assessed the relationship between the effects of AVP on tail skin temperature and the induced hypothermic response, and to determine if peripheral AVP administration increases heat loss from the tail. Core, BAT and tail skin temperature were monitored by telemetry in male Sprague–Dawley rats before and after intraperitoneal administration of AVP or vasopressin receptor antagonist. We also analyzed simultaneously of the time-course of AVP-induced hypothermic response and its relationship with changes in BAT temperature, and effect of AVP on grooming behavior. The key observations in this study were: (1) rats dosed with AVP induced a decrease in heat production (i.e., a reduction of BAT thermogenesis) and an increase of saliva spreading for evaporative heat loss (i.e., grooming behavior); (2) AVP caused a marked decrease in tail skin temperature and this effect was prevented by the peripheral administration of the vasopressin V1a receptor antagonist, suggesting that exogenous AVP does not increase heat loss in the tail of rats; (3) the vasopressin V1a receptor antagonist could elevate core temperature without affecting tail skin temperature, suggesting that endogenous AVP is involved in suppression of thermogenesis, but not mediates heat loss in the tail of rats. Overall, the present study does not support the conclusion of previous reports that AVP increased tail heat loss in rats, because AVP-induced hypothermia in the rat is accompanied by a decrease in tail skin temperature. The data indicate that exogenous AVP-induced hypothermia attributed to the suppression of thermoregulatory heat production and the increase of saliva spreading for evaporative heat loss. 相似文献
946.
Ahmed A. ElSharawy Guoyi Yang Xiaoping Hu 《Archives Of Phytopathology And Plant Protection》2013,46(8):646-663
Verticillium dahliae is one of the most important pathogens causing Verticillium wilt. We studied the characterisation of the genetic relationship between virulence, vegetative compatibility groups (VCGs) and inter-simple sequence repeat (ISSR). A total of 48 V. dahliae isolates, in which 16 are collected from different cotton growing regions in China and 4 isolates belonged to all known VCGs, are used. Half of them were found highly virulent. Mutants (565) were obtained using the nitrate non-utilising mutant. These mutants were grouped into three VCGs: VCG1 (27 isolates), VCG 2 (14 isolates) and VCG 3 (7 isolates). Use of ISSR indicated two main clusters that were related to VCG and virulence. Genetic diversity lineages were obviously correlated to VCGs and ISSRs according to their geographical origin, virulence and ISSR genetic variation. This study could be useful to design and develop effective management strategies beside for quarantine purposes on Verticillium wilt control. 相似文献
947.
Lei Liu Xu Yang Haoran Wang Guanglin Cui Yujun Xu Peihua Wang Gang Yuan Xiaojing Wang Hu Ding Dao Wen Wang 《Human genetics》2013,132(2):139-145
Recent publications have found an association between variants of exostosin 2 (EXT2) gene and the risk of type 2 diabetes in some population but not in others. In an attempt to address these inconsistencies, we investigated EXT2 variants in two independent cohorts, and conducted a literature-based meta-analysis. Through regression model, we assessed the relationship between the EXT2 single nucleotide polymorphisms (SNPs) (rs3740878, rs11037909 and rs1113132) and the risk of type 2 diabetes in Han Chinese population, including a total of 2,533 cases and 2,643 controls. We combined our data with that from previously published studies and performed a meta-analysis to evaluate the effect size of the gene. Consistent with some studies, we found marginal association for the rs3740878 (OR = 1.07, 95 % CI = 0.99, 1.16, p = 0.09), rs11037909 (OR = 1.07, 95 % CI = 0.99, 1.16, p = 0.08), and rs1113132 (OR = 1.08, 95 % CI = 1.00, 1.17, p = 0.06) in our 2 cohorts. Meta-analysis, comprising 9,224 type 2 diabetes and 10,484 controls, revealed that three SNPs (rs3740878, rs11037909 and rs1113132) in EXT2 were significantly associated with type 2 diabetes (ORs range from 1.06 to 1.07, p = 0.038, p = 0.008 and p = 0.005, respectively). Variation in the EXT2 locus appears to be associated with a small increase in the risk of type 2 diabetes. However, well-designed prospective studies with larger sample size and more ethnic groups are needed to further validate the results. 相似文献
948.
Jian-Guo Hu Xing-Jun Wu Yi-Fan Feng Gang-ming Xi Ling-Xiao Deng Zhen-Huan Wang Rui Wang Lin Shen Jian-Sheng Zhou He-Zuo Lü 《Neurochemical research》2013,38(3):601-609
The conditioned medium from B104 neuroblastoma cells (B104CM) induces proliferation of oligodendrocyte progenitor cells (OPCs) in vitro. However, the molecular events that occur during B104CM-induced proliferation of OPCs has not been well clarified. In the present study, using OPCs immunopanned from embryonic day 14 Sprague–Dawley rat spinal cords, we explored the activation of several signaling pathways and the expression of several important immediate early genes (IEGs) and cyclins in OPCs in response to B104CM. We found that B104CM can induce OPC proliferation through the activation of the extracellular signal-regulated kinases 1 and 2 (Erk1/2), but not PI3K or p38 MAPK signaling pathways in vitro. The IEGs involved in B104CM-induced OPC proliferation include c-fos, c-jun and Id2, but not c-myc, fyn, or p21. The cyclins D1, D2 and E are also involved in B104CM-stimulated proliferation of OPCs. The activation of Erk results in subsequent expression of IEGs (such as c-fos, c-jun and Id-2) and cyclins (including cyclin D1, D2 and E), which play key roles in cell cycle initiation and OPC proliferation. Collectively, these results suggest that the phosphorylation of Erk1/2 is an important molecular event during OPC proliferation induced by B104CM. 相似文献
949.
Yi Hong Juan Yang Xin Shen Huifen Zhu Xiaoxu Sun Xue Wen Jing Bian Heyu Hu Lu Yuan Juan Tao Ping Lei Guanxin Shen 《Cancer immunology, immunotherapy : CII》2013,62(3):447-454
Transferrin receptor (TfR) has been used as a target for the antibody-based therapy of cancer due to its higher expression in tumors relative to normal tissues. Great potential has been shown by anti-TfR antibodies combined with chemotherapeutic drugs as a possible cancer therapeutic strategy. In our study, we investigated the anti-tumor effects of anti-TfR monoclonal antibody (mAb) alone or in combination with sinomenine hydrochloride in vitro. Results suggested that anti-TfR mAb or sinomenine hydrochloride could induce apoptosis, inhibit proliferation, and affect the cell cycle. A synergistic effect was found in relation to tumor growth inhibition and the induction of apoptosis when anti-TfR mAb and sinomenine hydrochloride were used simultaneously. The expression of COX-2 and VEGF protein in HepG2 cells treated with anti-TfR mAb alone was increased in line with increasing dosage of the agent. In contrast, COX-2 expression was dramatically decreased in HepG2 cells treated with sinomenine hydrochloride alone. Furthermore, we demonstrated that the inhibitory effects of sinomenine hydrochloride and anti-TfR mAb administered in combination were more prominent than when the agents were administered singly. To sum up, these results showed that the combined use of sinomenine hydrochloride and anti-TfR mAb may exert synergistic inhibitory effects on human hepatoma HepG2 cells in a COX-2-dependent manner. This finding provides new insight into how tumor cells overcome the interference of iron intake to survive and forms the basis of a new therapeutic strategy involving the development of anti-TfR mAb combined with sinomenine hydrochloride for liver cancer. 相似文献
950.