全文获取类型
收费全文 | 6012篇 |
免费 | 556篇 |
国内免费 | 2篇 |
出版年
2023年 | 15篇 |
2022年 | 62篇 |
2021年 | 99篇 |
2020年 | 83篇 |
2019年 | 111篇 |
2018年 | 171篇 |
2017年 | 143篇 |
2016年 | 224篇 |
2015年 | 306篇 |
2014年 | 386篇 |
2013年 | 395篇 |
2012年 | 581篇 |
2011年 | 472篇 |
2010年 | 336篇 |
2009年 | 288篇 |
2008年 | 407篇 |
2007年 | 401篇 |
2006年 | 376篇 |
2005年 | 288篇 |
2004年 | 284篇 |
2003年 | 262篇 |
2002年 | 176篇 |
2001年 | 104篇 |
2000年 | 87篇 |
1999年 | 63篇 |
1998年 | 44篇 |
1997年 | 35篇 |
1996年 | 24篇 |
1995年 | 23篇 |
1994年 | 23篇 |
1993年 | 8篇 |
1992年 | 30篇 |
1991年 | 22篇 |
1990年 | 25篇 |
1989年 | 19篇 |
1988年 | 25篇 |
1987年 | 14篇 |
1986年 | 17篇 |
1985年 | 14篇 |
1984年 | 13篇 |
1983年 | 12篇 |
1982年 | 11篇 |
1981年 | 15篇 |
1980年 | 8篇 |
1979年 | 6篇 |
1978年 | 7篇 |
1976年 | 5篇 |
1973年 | 6篇 |
1972年 | 8篇 |
1965年 | 4篇 |
排序方式: 共有6570条查询结果,搜索用时 31 毫秒
941.
942.
Cyclin-dependent kinase (Cdk) inhibitor p21(Waf1/Cip1/Sdi1), a multifunctional protein, has a major role as tumor suppressor, mediating G1/S arrest through inhibition of Cdks. Recent biological studies of Cyclin D1/Cdk4 have proposed that p21 C-terminal domain (p21(CT)) plays a key role as a potent Cdk4 inhibitor. We report here solution structures of p21(CT) for both the free and Cdk4-bound forms using 2D transferred NOE spectroscopy and dynamical simulated annealing calculations. Even though p21(CT) peptide is very flexible in the free state, when it bound to Cdk4, the structure becomes well structured in the binding domain. Therefore we propose that p21(CT) experiences an extensive conformational change upon Cdk4 binding. This structural change of p21(CT) may suggest the molecular mechanism of p21 for specificity and inhibition mode to assemble different cyclin-Cdk complexes. Especially, our data suggests that the D(149)FYHSKRR(156) region of p21 is critical for Cdk4 binding, indicating that the major driving force for complex originates from hydrophobic interaction between p21 and Cdk4. 相似文献
943.
Ceramium inkyuii sp. nov. is newly described based on samples collected from the east coast of Korea and compared with similar species such as C. paniculatum and C. tenerrimum. The new species is characterized by pseudo‐dichotomously branched thalli with a twist in the upper part, a single row of spines on the abaxial side, strongly inrolled apices, and the presence of gland cells. In contrast, C. paniculatum has alternate branches and lacks gland cells, and C. tenerrimum is spineless and also lacks gland cells. Ceramium inkyuii was observed to be an annual species producing tetrasporangia in the spring to summer and cystocarps in the fall. Plastid‐encoded rbcL and nuclear small subunit (SSU) rDNA sequences were determined in four samples of C. inkyuii from different locations and six samples of four putative relatives. All four C. inkyuii replicates from three different locations had identical sequences of each gene, and the interspecific sequence divergences were enough to warrant its natural entity. The phylogenies of the rbcL and SSU rDNA sequences also indicate the monophyly of C. inkyuii. The spinous C. inkyuii was more closely related to the spineless C. tenerrimum than to the spinous C. paniculatum. 相似文献
944.
Joohon Sung Soo-Hun Cho Sung-Il Cho David L Duffy Jin-Hee Kim Ho Kim Kyung Sook Park Sue Kyung Park 《Twin research》2002,5(5):394-400
The Korean Twin Registry is the first nationwide twin study in Korea. We compiled 154,783 twin pairs from existing nation-wide data sources, mainly from address and national health insurance data. The coverage of this registry was almost complete for the twins born since 1970, but less complete as age increased, so that there were only 990 pairs who were born before 1930. The twins' health examination (N = 54,390 persons) and questionnaire (N = 44,546 persons) results were incorporated into the registry, yielding 12,894 and 9074 concordantly informative pairs. Morbidity and mortality outcomes have been followed up since 1990, for most diseases. For preliminary analysis of complex diseases, we selected ventricular septal defects (VSD) in young twins, stomach and colorectal cancers in adult twins. We identified 353 VSDs, 284 stomach cancers, and 116 colorectal cancers among twins. The prevalence rates of cancers, but not that of VSD, were lower in twins than those in population. The difference in the cancer prevalence was marked for twins born before 1926, implying some degree of selection. Like-sex (LS) twins showed familial recurrence risks (lambdaLS) of 41.2 for VSD and 22.4 for colorectal cancers, and 1.74 for stomach cancers. For opposite-sex (OS) twins, we could estimate lambdaOS of 19.8 for VSD only. These results were compatible with previous studies for VSD and colorectal cancers, but not for stomach cancers. Despite the strength in size, availability of health outcomes, and some lifestyle and basic laboratory data, we need accurate zygosity information to improve the validity of the results. 相似文献
945.
The protective adaptive response to electrophiles and reactive oxygen species is mediated by the induction of phase II detoxifying genes through antioxidant response elements (AREs). Our previous study showed that sulfur amino acid deprivation (SAAD) produces peroxides and induces rat glutathione S-transferase A2 (rGSTA2) through NF-E2-related factor 2 (Nrf2)/ARE activation via the pathway of phosphatidylinositol 3-kinase (PI3-kinase). The current study was designed to investigate the role of peroxynitrite in Nrf2/ARE activation and rGSTA2 induction. L-Arginine deficiency or N(G)-nitro-L-arginine methyl ester (L-NAME) reduced peroxide production induced by SAAD in H4IIE cells. Northern and Western blot analyses revealed that the levels of rGSTA2 mRNA and protein were significantly increased 24h after incubation of the cells in SAAD medium, which was inhibited by L-arginine deficiency or L-NAME. Subcellular fractionation and gel shift analyses revealed that SAAD increased the level of nuclear Nrf2 and activated ARE, which were also blocked by L-arginine deficiency or L-NAME. Whereas the exogenous NO donor S-nitroso-N-acetyl-penicillamine (SNAP) alone failed to significantly induce rGSTA2, SNAP enhanced SAAD-inducible rGSTA2 expression, verifying the notion that peroxynitrite derived from NO contributes to rGSTA2 induction. 3-Morpholinosydnonimine (SIN-1), which decomposes and yields peroxynitrite, increased the rGSTA2 mRNA and protein levels in a dose-dependent manner. SIN-1 increased the level of nuclear Nrf2 and activated Nrf2/ARE, which was supershifted by anti-Nrf2 and anti-Maf antibodies. SIN-1 increased the activity of PI3-kinase, as monitored by phosphorylation of Akt. SIN-1-inducible rGSTA2 expression was inhibited by PI3-kinase inhibitors. These results provide evidence that peroxynitrite plays an essential role in nuclear translocation of Nrf2 and ARE activation through the pathway of PI3-kinase and that nitric oxide synthase is involved in the induction of rGSTA2. 相似文献
946.
Kun-Pin Wu Jia-Ming Chang Jun-Bo Chen Chi-Fon Chang Wen-Jin Wu Tai-Huang Huang Ting-Yi Sung Wen-Lian Hsu 《Journal of computational biology》2006,13(2):229-244
We develop an iterative relaxation algorithm called RIBRA for NMR protein backbone assignment. RIBRA applies nearest neighbor and weighted maximum independent set algorithms to solve the problem. To deal with noisy NMR spectral data, RIBRA is executed in an iterative fashion based on the quality of spectral peaks. We first produce spin system pairs using the spectral data without missing peaks, then the data group with one missing peak, and finally, the data group with two missing peaks. We test RIBRA on two real NMR datasets, hbSBD and hbLBD, and perfect BMRB data (with 902 proteins) and four synthetic BMRB data which simulate four kinds of errors. The accuracy of RIBRA on hbSBD and hbLBD are 91.4% and 83.6%, respectively. The average accuracy of RIBRA on perfect BMRB datasets is 98.28%, and 98.28%, 95.61%, 98.16%, and 96.28% on four kinds of synthetic datasets, respectively. 相似文献
947.
Optimal Induction of Hepatitis C Virus Envelope-Specific Immunity by Bicistronic Plasmid DNA Inoculation with the Granulocyte-Macrophage Colony-Stimulating Factor Gene 总被引:12,自引:1,他引:11
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
In this study, we have constructed various DNA vaccine vectors that carried hepatitis C virus (HCV) envelope genes without and with the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene in several different ways. In Buffalo rats that received plasmids carrying the HCV envelope genes, which encode envelope proteins E1 and E2, both antibody and lymphoproliferative responses against these proteins were induced. These responses were greatly enhanced by the codelivery of the GM-CSF gene. In particular, inoculation with a bicistronic plasmid that independently expressed the GM-CSF gene and the envelope genes in the same construct generated the highest antibody titers and significantly increased lymphoproliferative responses against these proteins. Moreover, strong antibody responses to homologous and heterologous hypervariable region 1 peptides were elicited in the immunized rats. 相似文献
948.
Age-associated increase in PGE2 synthesis and COX activity in murine macrophages is reversed by vitamin E 总被引:8,自引:0,他引:8
Wu Dayong; Mura Casilda; Beharka Alison A.; Han Sung Nim; Paulson K. Eric; Hwang Daniel; Meydani Simin Nikbin 《American journal of physiology. Cell physiology》1998,275(3):C661
We previouslyshowed that increased macrophage andPGE2 production with age is due toenhanced cyclooxygenase (COX) activity and COX-2 expression. This studydetermined the effect of vitamin E supplementation on macrophagePGE2 synthesis in young and old mice and its underlying mechanism. Mice were fed 30 or 500 parts permillion vitamin E for 30 days. Lipopolysaccharide (LPS)-stimulated macrophages from old mice produced significantly morePGE2 than those from young mice.Vitamin E supplementation reversed the increasedPGE2 production in old mice buthad no effect on macrophage PGE2production in young mice. In both LPS-stimulated and unstimulated macrophages, COX activity was significantly higher in old than in youngmice at all intervals. Vitamin E supplementation completely reversedthe increased COX activity in old mice to levels comparable to those ofyoung mice but had no effect on macrophage COX activity of young miceor on COX-1 and COX-2 protein or COX-2 mRNA expression in young or oldmice. Thus vitamin E reverses the age-associated increase in macrophagePGE2 production and COX activity.Vitamin E exerts its effect posttranslationally, by inhibiting COXactivity. 相似文献
949.
A medium which contained 3% NaCl and 0.2% Teepol in 1/15 M phosphate buffer was prepared and was evaluated to be a useful enrichment medium for the isolation of Vibrio parahaemolyticus in marine specimens. Glucose salt Teepol broth produced a poorer result than direct culture. 相似文献
950.