全文获取类型
收费全文 | 10135篇 |
免费 | 851篇 |
国内免费 | 897篇 |
出版年
2024年 | 21篇 |
2023年 | 144篇 |
2022年 | 318篇 |
2021年 | 581篇 |
2020年 | 410篇 |
2019年 | 460篇 |
2018年 | 452篇 |
2017年 | 294篇 |
2016年 | 436篇 |
2015年 | 681篇 |
2014年 | 749篇 |
2013年 | 797篇 |
2012年 | 902篇 |
2011年 | 781篇 |
2010年 | 534篇 |
2009年 | 434篇 |
2008年 | 545篇 |
2007年 | 468篇 |
2006年 | 419篇 |
2005年 | 334篇 |
2004年 | 274篇 |
2003年 | 257篇 |
2002年 | 196篇 |
2001年 | 176篇 |
2000年 | 151篇 |
1999年 | 174篇 |
1998年 | 91篇 |
1997年 | 83篇 |
1996年 | 79篇 |
1995年 | 79篇 |
1994年 | 97篇 |
1993年 | 52篇 |
1992年 | 53篇 |
1991年 | 67篇 |
1990年 | 42篇 |
1989年 | 49篇 |
1988年 | 32篇 |
1987年 | 26篇 |
1986年 | 34篇 |
1985年 | 25篇 |
1984年 | 16篇 |
1983年 | 12篇 |
1982年 | 10篇 |
1981年 | 5篇 |
1980年 | 5篇 |
1978年 | 4篇 |
1973年 | 4篇 |
1970年 | 3篇 |
1969年 | 3篇 |
1968年 | 4篇 |
排序方式: 共有10000条查询结果,搜索用时 234 毫秒
851.
852.
Shi YX Chen Y Zhu YZ Huang GY Moore PK Huang SH Yao T Zhu YC 《American journal of physiology. Heart and circulatory physiology》2007,293(4):H2093-H2100
Hydrogen sulfide (H(2)S) is a gasotransmitter that regulates cardiovascular functions. The present study aimed to examine the hypothesis that chronic treatment with sodium hydrosulfide (NaHS, an H(2)S donor) is able to prevent left-ventricular remodeling in spontaneously hypertensive rats (SHR). Four-week-old SHR were treated with NaHS (10, 30, and 90 micromol x kg(-1) x day(-1)), a combination of NaHS (30 micromol x kg(-1) x day(-1)) and glibenclamide (5 mg x kg(-1) x day(-1)), glibenclamide alone (5 mg x kg(-1) x day(-1)), hydralazine alone (10 mg x kg(-1) x day(-1)), and placebo for 3 mo. At the end of the treatment period, variables such as cardiac geometry and function, intramyocardial arterioles ranging in diameter from 25 to 100 microm, perivascular and interstitial collagen content, reactive oxygen species (ROS), thiol groups, conjugated dienes, and DNA base modification were examined. The novel finding of the present study is that chronic NaHS treatment prevented the hypertrophy of intramyocardial arterioles and ventricular fibrosis, as well as decreased myocardial ROS and conjugated diene levels. The cardioprotective effects were blunted by coadministration of glibenclamide, suggesting a role of ATP-sensitive potassium channels in mediating the action of NaHS. Hydralazine caused a comparable reduction of blood pressure compared with NaHS treatment; however, it exerted no effect on the remodeling process or on ROS and conjugated diene levels. Moreover, NaHS treatment caused an increase in myocardial thiol group levels, whereas DNA base modification was not altered by NaHS treatment. In conclusion, the superior cardioprotective effects of NaHS treatment are worthy to be further explored to develop novel therapeutic approaches for the treatment of cardiac remodeling in hypertension. 相似文献
853.
西藏雪灵芝促进消化作用实验研究 总被引:1,自引:0,他引:1
目的:探讨雪灵芝是否具有促进消化的功效。方法:选用雄性大鼠和小鼠各一批:①大鼠灌胃给不同剂量的雪灵芝提取浓缩液和蒸馏水一个月后进行消化酶的测定;并计算体重增重量、摄食量及食物利用率。②小鼠灌胃给不同剂量的雪灵芝提取浓缩液和蒸馏水(2个对照组)15d后进行小肠运动实验。结果:①雪灵芝各剂量组大鼠体重增重量均高于阴性对照组,高、中剂量组与阴性对照组的差异具有显著性(P〈0.05)。各剂量组的食物利用率均高于阴性对照组,且高、中剂量组与阴性对照组的差异有显著性(P〈0.05)。②雪灵芝各剂量组小鼠的墨汁推进率均高于便秘模型对照组,且差异均显著或非常(P〈0.01或P〈0.05)。结论:雪灵芝具有促进消化功能的功效。 相似文献
854.
During cell division, chromosome segregation is orchestrated by the interaction of spindle microtubules with thecentromere. A dramatic remodeling of interpolar microtubules into an organized central spindle between the separatingchromatids is required for the initiation and execution of cytokinesis. Central spindle organization requires mitotic kine-sins, the chromosomal passenger protein complex, and microtubule bundling protein PRC1. PRC1 is phosphorylated byCdc2 at Thr470 and Thr481 during mitosis. However, the functional relevance of PRC1 phosphorylation at Thr470 hasremained elusive. Here we show that expression of the non-phosphorylatable mutant PRC1~(T470A) but not the phospho-mimi-cking mutant PRC1~(T470E) causes aberrant organization of the central spindle. Immunoprecipitation experiment indicatesthat both PRC1~(T470A) and PRC1~(T470E) mutant proteins associate with wild-type PRC1, suggesting that phosphorylationof Thr470 does not alter PRC1 self-association. In addition, in vitro co-sedimentation experiment showed that PRC1binds to microtubule independent of the phosphorylation state of Thr470. Gel-filtration experiment suggested that phos-phorylation of Thr470 promotes oligomerization of PRC1. Given the fact that prevention of the Thr470 phosphorylationinhibits PRC1 oligomerization in vitro and causes an aberrant organization of central spindle in vivo, we propose thatthis phosphorylation-dependent PRC1 oligomerization ensures that central spindle assembly occurs at the appropriatetime in the cell cycle. 相似文献
855.
856.
857.
Mai Li Shanjing Yao Kazuyuki Shimizu 《World journal of microbiology & biotechnology》2007,23(4):573-580
The effect of poxB gene knockout on metabolism in Escherichia coli was investigated in the present paper based on the growth characteristics and the activities of the enzymes involved in the
central metabolic pathways. The absence of pyruvate oxidase reduced the glucose uptake rate and cell growth rate, and increased
O2 consumption and CO2 evolution. The enzyme assay results showed that although glucokinase activity increased, the flux through glycolysis was
reduced due to the down-regulation of the other glycolytic enzymes such as 6-phosphofructosekinase and fructose bisphosphate
aldolase in the poxB mutant. TCA cycle enzymes such as citrate synthase and malate dehydrogenase were repressed in the poxB mutant when the cells were cultivated in LB medium. The pyruvate oxidase mutation also resulted in the activation of glucose-6-phosphate
dehydrogenase and acetyl-CoA synthetase. All these results suggest that pyruvate oxidase is not only a stationary-phase enzyme
as previously known, and that the removal of the poxB gene affects the central metabolism at the enzyme level in E. coli. 相似文献
858.
Spina CS Ton L Yao M Maehr H Wolfe MM Uskokovic M Adorini L Holick MF 《The Journal of steroid biochemistry and molecular biology》2007,103(3-5):757-762
The active form of vitamin D, 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], is an endocrine hormone whose classic role is the maintenance of calcium homeostasis. It is well documented that 1,25(OH)(2)D(3) also has anti-tumor effects on a number of cancers and cancer cell lines including breast, colorectal, gastric, liver, ovarian, prostate, and non-melanoma skin cancers. Included in the anti-tumor activities of 1,25(OH)(2)D(3) are its ability to cause antiproliferation, prodifferentation and decrease angiogenesis. Furthermore, through regulation of the plaminogen activator (PA) system and a class of proteolytic enzymes called matrix metalloproteinases (MMPs), 1,25(OH)(2)D(3) reduces the invasive spread of tumor cells. Because of the calcemic limitations of using 1,25(OH)(2)D(3) as a therapy, we have tested the effects of a novel Gemini vitamin D analogue, Deuterated Gemini (DG), on mouse colorectal cancer. We demonstrated that DG is more potent in reducing tumor volume and mass, compared to control and 1,25(OH)(2)D(3). DG significantly prevented (100% reduction, p<0.05) the invasive spread of colorectal tumor cells into the surrounding muscle, and had no effect on serum calcium levels. Thus, DG acts as a selective vitamin D receptor modulator (SVDRM) by enhancing select anti-tumor characteristic 1,25(OH)(2)D(3) activities, without inducing hypercalcemia. Thus, DG shows promise in the development of colorectal cancer therapies. 相似文献
859.
Conjugation of the methyl group at the fifth carbon of cytosines within the palindromic dinucleotide 5'-CpG-3' sequence (DNA methylation) is the best studied epigenetic mechanism, which acts together with other epigenetic entities: histone modification, chromatin remodeling and microRNAs to shape the chromatin structure of DNA according to its functional state. The cancer genome is frequently characterized by hypermethylation of specific genes concurrently with an overall decrease in the level of 5-methyl cytosine, the pathological implication of which to the cancerous state has been well established. While the latest genome-wide technologies have been applied to classify and interpret the epigenetic layer of gene regulation in the physiological and disease states, the epigenetic testing has also been seriously explored in clinical practice for early detection, refining tumor staging and predicting disease recurrence. This critique reviews the latest research findings on the use of DNA methylation in cancer diagnosis, prognosis and staging/classification. 相似文献
860.
The p13 gene is uniquely present in Group II nucleopolyhedroviruses (NPVs) and some granuloviruses, but not in Group I NPVs. p13 gene was first described by our laboratory in Leucania separatamultiple nuclear polyhedrosis virus (Ls-p13) in 1995. However, the functions of Ls-P13 and of its homologues are unknown. When Ls-p13 was inserted into Autographa californica nucleopolyhedrovirus, a Group I NPV, polyhedra yield was inhibited. However, this inhibition was prevented when the leucine zipper-like domain of Ls-p13 was mutated. To determine the cause of this marked difference between Ls-P13 and leucine zipper mutated Ls-P13 (Ls-P13mL), oligomerization and secondary structure analyses were performed. High performance liquid chromatography and yeast two-hybrid assays indicated that neither Ls-P13 nor Ls-P13mL could form oligomers. Informatics and circular dichroism spectropolarimetry results further indicated marked secondary structural differences between Ls-P13 and Ls-P13mL. The LZLD of Ls-P13 has two extended heptad repeat units which form a hydrophobic surface, but it is short of a third hydrophobic heptad repeat unit for oligomerization. However, the mutated LZLD of Ls-P13mL lacks the above hydrophobic surface, and its secondary structure is markedly different. This difference in its secondary structure may explain why Ls-P13mL is unable to inhibit polyhedra yield. 相似文献