全文获取类型
收费全文 | 488篇 |
免费 | 20篇 |
专业分类
508篇 |
出版年
2023年 | 5篇 |
2022年 | 10篇 |
2021年 | 23篇 |
2020年 | 9篇 |
2019年 | 18篇 |
2018年 | 21篇 |
2017年 | 10篇 |
2016年 | 25篇 |
2015年 | 23篇 |
2014年 | 21篇 |
2013年 | 33篇 |
2012年 | 43篇 |
2011年 | 46篇 |
2010年 | 24篇 |
2009年 | 26篇 |
2008年 | 29篇 |
2007年 | 23篇 |
2006年 | 20篇 |
2005年 | 21篇 |
2004年 | 29篇 |
2003年 | 16篇 |
2002年 | 12篇 |
2001年 | 3篇 |
2000年 | 2篇 |
1999年 | 5篇 |
1998年 | 4篇 |
1996年 | 1篇 |
1992年 | 1篇 |
1991年 | 1篇 |
1990年 | 1篇 |
1989年 | 1篇 |
1988年 | 2篇 |
排序方式: 共有508条查询结果,搜索用时 15 毫秒
31.
Nitrogen and Phosphorus Limitation of Phytoplankton Growth in New Zealand Lakes: Implications for Eutrophication Control 总被引:6,自引:0,他引:6
We examine macronutrient limitation in New Zealand (NZ) lakes where, contrary to the phosphorus (P) only control paradigm,
nitrogen (N) control is widely adopted to alleviate eutrophication. A review of published results of nutrient enrichment experiments
showed that N more frequently limited lake productivity than P; however, stoichiometric analysis of a sample of 121 NZ lakes
indicates that the majority (52.9%) of lakes have a mean ratio of total nitrogen (TN) to total phosphorus (TP) (by mass) indicative
of potential P-limitation (>15:1), whereas only 14.0% of lakes have mean TN:TP indicative of potential N-limitation (<7:1).
Comparison of TN, TP, and chlorophyll a data between 121 NZ lakes and 689 lakes in 15 European Union (EU) countries suggests that at the national scale, N has a
greater role in determining lake productivity in NZ than in the EU. TN:TP is significantly lower in NZ lakes across all trophic
states, a difference that is driven primarily by significantly lower in-lake TN concentrations at low trophic states and significantly
higher TP concentrations at higher trophic states. The form of the TN:TP relationship differs between NZ and the EU countries,
suggesting that lake nutrient sources and/or loss mechanisms differ between the two regions. Dual control of N and P should
be the status quo for lacustrine eutrophication control in New Zealand and more effort is needed to reduce P inputs. 相似文献
32.
Here we report the association of the rs694539 variant of nicotinamide-N-methyltransferase gene with bipolar disorder in a case–control study of 95 bipolar disorder patients and 201 healthy controls (χ2 = 13.382, P = 0.001). With the polymerase chain reaction restriction fragment length polymorphism method we developed we were able to show the association for the first time. This new finding may provide evidence to understand the mechanism of the disease. 相似文献
33.
Sanaz Gabery Nellie Georgiou-Karistianis Sofia Hult Lundh Rachel Y. Cheong Andrew Churchyard Phyllis Chua Julie C. Stout Gary F. Egan Deniz Kirik ?sa Petersén 《PloS one》2015,10(2)
Huntington disease (HD) is a fatal neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin gene. Non-motor symptoms and signs such as psychiatric disturbances, sleep problems and metabolic dysfunction are part of the disease manifestation. These aspects may relate to changes in the hypothalamus, an area of the brain involved in the regulation of emotion, sleep and metabolism. Neuropathological and imaging studies using both voxel-based morphometry (VBM) of magnetic resonance imaging (MRI) as well as positron emission tomography (PET) have demonstrated pathological changes in the hypothalamic region during early stages in symptomatic HD. In this investigation, we aimed to establish a robust method for measurements of the hypothalamic volume in MRI in order to determine whether the hypothalamic dysfunction in HD is associated with the volume of this region. Using T1-weighted imaging, we describe a reproducible delineation procedure to estimate the hypothalamic volume which was based on the same landmarks used in histologically processed postmortem hypothalamic tissue. Participants included 36 prodromal HD (pre-HD), 33 symptomatic HD (symp-HD) and 33 control participants who underwent MRI scanning at baseline and 18 months follow-up as part of the IMAGE-HD study. We found no evidence of cross-sectional or longitudinal changes between groups in hypothalamic volume. Our results suggest that hypothalamic pathology in HD is not associated with volume changes. 相似文献
34.
Salman F Erten G Unal M Kiran B Salman S Deniz G Yilmaz MT Kayserilioglu A Dinccag N 《Acta physiologica Hungarica》2008,95(1):77-86
The essential therapy of diabetes mellitus includes medical nutrition therapy (MNT), exercise and medical therapy. Exercise, besides its metabolic effects, has positive influence on the immune system, but some forms of exercise may cause trauma for muscle and skeletal systems, they may also support negative effects on the immune system. Nineteen type 1 diabetic patients (mean age 22.1 +/- 2.8 yrs), followed by Diabetes Outpatient Clinic and twenty age matched male control subjects were included into the study, to demonstrate the effects of maximal, acute exercise on the immune system. The exercise test was performed according to Bruce protocol on treadmill. In diabetic subjects, increased CD19 and CD23 expressions were observed before exercise. In both groups (diabetic/control) CD3, CD4 expressions and CD4/CD8 ratio were decreased following the exercise, however expression of natural killer (NK) cells increased. Compared to type 1 diabetic patients healthy subjects had longer acute exercise that caused the increased level of CD8 expression, however type 1 diabetic patients did not show any difference. These results indicate that submaximal aerobic exercise might be recommended for type 1 diabetics without any complications because of its positive reflection on metabolic control and no negative effects on the immune system. 相似文献
35.
Michaela Ihle Stephanie Biber Insa S Schroeder Christine Blattner Miriam Deniz Giovanna Damia Vanesa Gottifredi Lisa Wiesmüller 《Nucleic acids research》2021,49(13):7457
Using human embryonic, adult and cancer stem cells/stem cell-like cells (SCs), we demonstrate that DNA replication speed differs in SCs and their differentiated counterparts. While SCs decelerate DNA replication, differentiated cells synthesize DNA faster and accumulate DNA damage. Notably, both replication phenotypes depend on p53 and polymerase iota (POLι). By exploring protein interactions and newly synthesized DNA, we show that SCs promote complex formation of p53 and POLι at replication sites. Intriguingly, in SCs the translocase ZRANB3 is recruited to POLι and required for slow-down of DNA replication. The known role of ZRANB3 in fork reversal suggests that the p53–POLι complex mediates slow but safe bypass of replication barriers in SCs. In differentiated cells, POLι localizes more transiently to sites of DNA synthesis and no longer interacts with p53 facilitating fast POLι-dependent DNA replication. In this alternative scenario, POLι associates with the p53 target p21, which antagonizes PCNA poly-ubiquitination and, thereby potentially disfavors the recruitment of translocases. Altogether, we provide evidence for diametrically opposed DNA replication phenotypes in SCs and their differentiated counterparts putting DNA replication-based strategies in the spotlight for the creation of therapeutic opportunities targeting SCs. 相似文献
36.
zlem Alptekin S. Seyhan Tükel Deniz Yldrm Dilek Alagz 《Journal of Molecular Catalysis .B, Enzymatic》2009,58(1-4):124-131
Bovine liver catalase was covalently immobilized onto controlled pore glass (CPG) beads modified with 3-aminopropyltriethoxysilane (3-APTES) followed by treatment with glutaraldehyde. Coupling of catalase onto CPG was optimized to improve the efficiency of the overall immobilization procedure. The optimum coupling conditions: pore diameter of CPG, pH, buffer concentration, temperature, coupling time and initial catalase amount per grams of carrier were determined as 70 nm, 6.0, 75 mM, 5 °C, 7 h and 6 mg catalase, respectively. Catalytic efficiencies (kcat/Km) and thermal inactivation rate constants (ki) of ICPG1 were determined and compared with that of free catalase. Suitability of ICPG1 was also investigated by using it in batch and plug-flow type reactors. When the remaining activity of ICPG1 retained was about 50% of its initial activity the highest total productivity of ICPG1 was determined as 7.6 × 106 U g immobilized catalase−1 in plug-flow type reactor. However, the highest total productivity of ICPG1 was 6.2 × 105 U g immobilized catalase−1 in batch type reactor. ICPG1 may have great potentials as biocatalyst for the application in decomposition of hydrogen peroxide in plug-flow type reactor. 相似文献
37.
Deniz Ekİncİ Şükrü Beydemir Ö. İrfan Küfrevİoğlu 《Journal of enzyme inhibition and medicinal chemistry》2013,28(6):745-750
The inhibition of two human carbonic anhydrase (HCA, EC 4.2.1.1) isozymes, the cytosolic HCA I and II, with heavy metal salts of Pb(II), Co(II) and Hg(II)has been investigated. Human erythrocyte CA-I isozyme was purified with a specific activity of 920 EUmg? 1 and a yield of 30% and CA-II isozyme was purified with a specific activity of 8000 EUmg? 1 and a yield of 40% using Sepharose-4B-L tyrosine-sulfanilamide affinity gel chromatography. The overall purification was approximately 104-fold for HCA-I and 900-fold for HCA-II. The inhibitory effects of different heavy metals (lead, cobalt and mercury) on CA activity were determined at low concentrations using the esterase method under in vitro conditions. Ki values for these metals were calculated from Lineweaver-Burk graphs as 1.0, 3.22 and 1.45 mM for HCA-I and 0.059, 1.382 and 0.32 mM for HCA-II respectively. Lead was a noncompetitive inhibitor for HCA-I and competitive for HCA-II, cobalt was competitive for HCA-I and noncompetitive for HCA-II and mercury was uncompetitive for both HCA-I and HCA-II. Lead was the best inhibitor for both HCA-I and HCA-II. 相似文献
38.
Gonon AT Erbas D Bröijersén A Valen G Pernow J 《American journal of physiology. Heart and circulatory physiology》2004,286(5):H1767-H1774
Endothelin (ET) receptor antagonism protects from ischemia-reperfusion injury. We hypothesized that the cardioprotective effect is related to nitric oxide (NO) bioavailability. Buffer-perfused rat and mouse hearts were subjected to ischemia and reperfusion. At the onset of ischemia, the rat hearts received vehicle, the dual endothelin type A/type B (ETA/ETB) receptor antagonist bosentan (10 microM), the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA; 100 microM), the combination of bosentan and L-NMMA or the combination of bosentan, L-NMMA, and the NO substrate L-arginine (1 mM). Hearts from wild-type and endothelial NO synthase (eNOS)-deficient mice received either vehicle or bosentan. Myocardial performance, endothelial function, NO outflow, and eNOS expression were monitored. Bosentan significantly improved myocardial function during reperfusion in rats and in wild-type mice, but not in eNOS-deficient mice. The functional protection afforded by bosentan was inhibited by L-NMMA, whereas it was restored by L-arginine. Myocardial expression of eNOS (immunoblotting) increased significantly in bosentan-treated rat hearts compared with vehicle hearts. Recovery of NO outflow during reperfusion was enhanced in the bosentan-treated rat heart. The endothelium-dependent vasodilator adenosine diphosphate increased coronary flow by 18 +/- 9% at the end of reperfusion in the bosentan group, whereas it reduced coronary flow by 7 +/- 5% in the vehicle group (P < 0.001). The response to the endothelium-independent dilator sodium nitroprusside was not different between the two groups. In conclusion, the dual ETA/ETB receptor antagonist bosentan preserved endothelial and cardiac contractile function during ischemia and reperfusion via a mechanism dependent on endothelial NO production. 相似文献
39.
Top D de Antueno R Salsman J Corcoran J Mader J Hoskin D Touhami A Jericho MH Duncan R 《The EMBO journal》2005,24(17):2980-2988
Biological membrane fusion is dependent on protein catalysts to mediate localized restructuring of lipid bilayers. A central theme in current models of protein-mediated membrane fusion involves the sequential refolding of complex homomeric or heteromeric protein fusion machines. The structural features of a new family of fusion-associated small transmembrane (FAST) proteins appear incompatible with existing models of membrane fusion protein function. While the FAST proteins function to induce efficient cell-cell fusion when expressed in transfected cells, it was unclear whether they function on their own to mediate membrane fusion or are dependent on cellular protein cofactors. Using proteoliposomes containing the purified p14 FAST protein of reptilian reovirus, we now show via liposome-cell and liposome-liposome fusion assays that p14 is both necessary and sufficient for membrane fusion. Stoichiometric and kinetic analyses suggest that the relative efficiency of p14-mediated membrane fusion rivals that of the more complex cellular and viral fusion proteins, making the FAST proteins the simplest known membrane fusion machines. 相似文献
40.
Ferah Budak S. Haldun Bal Gulcin Tezcan Furkan Guvenc E. Halis Akalin Guher Goral Gunnur Deniz H. Barbaros Oral 《PloS one》2016,11(11)
Although our knowledge about Brucella virulence factors and the host response increase rapidly, the mechanisms of immune evasion by the pathogen and causes of chronic disease are still unknown. Here, we aimed to investigate the immunological factors which belong to CD8+ T cells and their roles in the transition of brucellosis from acute to chronic infection. Using miRNA microarray, more than 2000 miRNAs were screened in CD8+ T cells of patients with acute or chronic brucellosis and healthy controls that were sorted from peripheral blood with flow cytometry and validated through qRT-PCR. Findings were evaluated using GeneSpring GX (Agilent) 13.0 software and KEGG pathway analysis. Expression of two miRNAs were determined to display a significant fold change in chronic group when compared with acute or control groups. Both miRNAs (miR-126-5p and miR-4753-3p) were decreased (p <0.05 or fold change > 2). These miRNAs have the potential to be the regulators of CD8+ T cell-related marker genes for chronic brucellosis infections. The differentially expressed miRNAs and their predicted target genes are involved in MAPK signaling pathway, cytokine-cytokine receptor interactions, endocytosis, regulation of actin cytoskeleton, and focal adhesion indicating their potential roles in chronic brucellosis and its progression. It is the first study of miRNA expression analysis of human CD8+ T cells to clarify the mechanism of inveteracy in brucellosis. 相似文献