全文获取类型
收费全文 | 691篇 |
免费 | 58篇 |
出版年
2022年 | 4篇 |
2021年 | 4篇 |
2020年 | 6篇 |
2019年 | 7篇 |
2018年 | 9篇 |
2017年 | 10篇 |
2016年 | 14篇 |
2015年 | 14篇 |
2014年 | 21篇 |
2013年 | 47篇 |
2012年 | 31篇 |
2011年 | 28篇 |
2010年 | 20篇 |
2009年 | 12篇 |
2008年 | 30篇 |
2007年 | 29篇 |
2006年 | 39篇 |
2005年 | 34篇 |
2004年 | 29篇 |
2003年 | 24篇 |
2002年 | 17篇 |
2001年 | 21篇 |
2000年 | 24篇 |
1999年 | 17篇 |
1998年 | 18篇 |
1997年 | 5篇 |
1996年 | 7篇 |
1995年 | 13篇 |
1994年 | 16篇 |
1993年 | 4篇 |
1992年 | 12篇 |
1991年 | 19篇 |
1990年 | 13篇 |
1989年 | 14篇 |
1988年 | 12篇 |
1987年 | 12篇 |
1986年 | 7篇 |
1985年 | 11篇 |
1984年 | 11篇 |
1983年 | 7篇 |
1982年 | 6篇 |
1980年 | 4篇 |
1979年 | 18篇 |
1976年 | 4篇 |
1975年 | 4篇 |
1974年 | 7篇 |
1973年 | 8篇 |
1972年 | 8篇 |
1971年 | 4篇 |
1970年 | 5篇 |
排序方式: 共有749条查询结果,搜索用时 15 毫秒
51.
Fmoc-protected Phe-Gly-type (Z)-alkene dipeptide isostere (ADI) and (E)-fluoroalkene dipeptide isostere (FADI) were synthesized and applied to Fmoc-based solid-phase peptide synthesis (SPPS). These cis-peptide bond mimetics were introduced into a bioactive pentapeptide [H-Amb-Phe-Gly-Leu-Arg-Trp-NH(2); Amb = 4-(aminomethyl) benzoic acid], which has potent GPR54 agonistic activity. The resulting pentapeptide derivatives showed low GPR54 agonistic activity, as compared with the parent peptide and (E)-ADI-containing derivative. This suggests that the trans-amide conformer of Phe-Gly peptide bond of the parent peptide would be significantly important for bioactivity. Contrary to our expectations, a (Z)-FADI-containing derivative exhibited essentially no activity, revealing the necessity of critical validation of FADI-bioisosterism. 相似文献
52.
Takeda N Maemura K Horie S Oishi K Imai Y Harada T Saito T Shiga T Amiya E Manabe I Ishida N Nagai R 《The Journal of biological chemistry》2007,282(45):32561-32567
Cardiovascular diseases are closely related to circadian rhythm, which is under the control of an internal biological clock mechanism. Although a biological clock exists not only in the hypothalamus but also in each peripheral tissue, the biological relevance of the peripheral clock remains to be elucidated. In this study we searched for clock-controlled genes in vascular endothelial cells using microarray technology. The expression of a total of 229 genes was up-regulated by CLOCK/BMAL2. Among the genes that we identified, we examined the thrombomodulin (TM) gene further, because TM is an integral membrane glycoprotein that is expressed primarily in vascular endothelial cells and plays a major role in the regulation of intravascular coagulation. TM mRNA and protein expression showed a clear circadian oscillation in the mouse lung and heart. Reporter analyses, gel shift assays, and chromatin immunoprecipitation analyses using the TM promoter revealed that a heterodimer of CLOCK and BMAL2 binds directly to the E-box of the TM promoter, resulting in TM promoter transactivation. Indeed, the oscillation of TM gene expression was abolished in clock mutant mice, suggesting that TM expression is regulated by the clock gene in vivo. Finally, the phase of circadian oscillation of TM mRNA expression was altered by temporal feeding restriction, suggesting TM gene expression is regulated by the peripheral clock system. In conclusion, these data suggest that the peripheral clock in vascular endothelial cells regulates TM gene expression and that the oscillation of TM expression may contribute to the circadian variation of cardiovascular events. 相似文献
53.
Michinori Tanaka Shinya Oishi Hiroaki Ohno Nobutaka Fujii 《International journal of peptide research and therapeutics》2007,13(1-2):271-279
A reliable method for solid-phase synthesis of peptide aldehydes by using a new oxazolidine linker is described. Based on
a comparative study using the usual cleavage protocol as is used for the Fmoc-based peptide synthesis, we found that this
new linker is more appropriate for the synthesis of peptide aldehydes compared with the precedent acetal, semicarbazone or
threonine linker. Whereas N-Acylated oxazolidines might be partially deprotected to non-N-acylated intermediates in the TFA cocktail containing several soft nucleophiles which cause significant side reactions, the
new oxazolidine linker could produce the desired peptide aldehydes by simple Et2O washing and subsequent aqueous workup in high chemical yields and purity. We demonstrate the new method is useful especially
for the preparation of highly functionalized long-chain peptide aldehydes which require several scavenger chemicals in the
final deprotection step.
This paper is dedicated to the memory of the late Prof. R. Bruce Merrifield, who passed away May 14, 2006. 相似文献
54.
55.
Aki Tomizawa Kazuhiro Nogawa Yuuka Watanabe Mitsuhiro Oishi Kumihiko Tanaka Kouichi Sakata 《Chronobiology international》2019,36(6):751-757
We investigated how differences in circadian rhythm type affect the health of workers engaged in shift work. Employees, who were newly hired in a steel company between 2007 and 2011, received the Morningness–Eveningness Questionnaire (MEQ) survey. The target participants were 153 male shift workers who were not being treated with any antihyperlipidemic drugs and underwent periodic physical examinations including blood tests at least twice. According to the score of the MEQ at the time of joining the company, we classified the subjects into five types. Longitudinal changes in serum lipid level were estimated among the circadian rhythm types adjusted for age, BMI, and other covariates using a linear mixed model. The regression coefficient of total cholesterol level in the “definitely and moderately morning” group was ?17.83 (95% confidence interval (CI): ?33.42 to ?2.23), and in the “intermediate ‘group’ was ?16.84 [95% CI: ?30.40 to ?3.28], compared to the moderate evening type.” The total cholesterol level was higher in the moderately evening type than in any of the other groups. Between the Morningness–Eveningness (ME) type and Low-density lipoprotein (LDL) cholesterol levels, compared with the “moderately evening type” group, the regression coefficient in the “intermediate type” group was ?16.08 (95% CI: ?28.79 to ?3.37), and in the “definitely and moderately morning type” group was ?17.50 [95% CI: ?32.11 to ?2.88]. The “moderately evening type” group had a higher LDL cholesterol level than any of the other groups. Evening-type circadian rhythm type shift workers are more prone to elevated serum lipid levels. 相似文献
56.
Michael Ulyshen Katherine Elliott Joel Scott Scott Horn Patsy Clinton Ning Liu Chelcy F. Miniat Peter Caldwell Chris Oishi Jennifer Knoepp Paul Bolstad 《Ecology and evolution》2022,12(3)
Rhododendron maximum is an evergreen shrub native to the Appalachian Mountains of North America that has expanded in recent decades due to past disturbances and land management. The purpose of this study was to explore how bees and plants were affected by the experimental removal of R. maximum followed by a prescribed fire in one watershed compared to a neighboring reference watershed. Bees and plants were sampled for three years in both watersheds. Comparisons were based on the rarefaction and extrapolation sampling curves of Hill numbers as well as multivariate methods to assess effects on community composition. Bee richness, Shannon''s diversity, and Simpson''s diversity did not differ between watersheds in the year after removal but were all significantly higher in the removal watershed in year two, following the prescribed fire. Bee Shannon''s diversity and Simpson''s diversity, but not richness, remained significantly higher in the removal watershed in the third year. Similar but weaker patterns were observed for plants. Comparisons of community composition found significant differences for bees in the second and third year and significant differences for plants in all three years. For both groups, significant indicator taxa were mostly associated with the removal watershed. Because bees appeared to respond more strongly to the prescribed fire than to the removal of R. maximum and these benefits weakened considerably one year after the fire, clearing R. maximum does not appear to dramatically improve pollinator habitat in the southern Appalachians. This conclusion is underscored by the fact that about one quarter of the bee species in our study area were observed visiting R. maximum flowers. The creation of open areas with wildflowers may be a better way to benefit bees in this region judging from the high diversity of bees captured in the small roadside clearings in this study. 相似文献
57.
Disruption of phospholipase B gene, PLB1, increases the survival of baker's yeast Torulaspora delbrueckii 总被引:2,自引:0,他引:2
Abstract An uracil auxotrophic mutant of baker's yeast Torulaspora delbrueckii , which is resitant to 5-fluoro-orotic acid, was complemented by transformation with YEp24 which harbors 2 μm origin and URA3 derived from Saccharomyces cerevisiae . The phospholipase B in T. delbrueckii cells is active in both acidic and alkaline conditions. However, activity of phospholipase B gene ( PLB1 ) in cells of disruption mutant ( plbI : : URA3 ) was lost in both conditions, which indicates that all phospholipase B activity is encoded by a single gene (or a single polypeptide) in these yeast cells. Over-expression of PLB1 with YEp plasmid vector in T. delbrueckii cells showed ∼ 2.5-fold increase in phospholipase B activity, comparing with that in wild-type cells. Cells of plb1 Δ mutant showed increased survival when cells of plb1 Δ mutant and wild-type strain were incubated in water at 30 °C. Cells of PLB1 -over-expressed strain died rapidly even during the cultivation period, indicating that phospholipase B activity may be a determinant for the survival of this yeast. 相似文献
58.
Three types of polymorphisms in exon 14 in porcine Mx1 gene 总被引:8,自引:0,他引:8
Morozumi T Sumantri C Nakajima E Kobayashi E Asano A Oishi T Mitsuhashi T Watanabe T Hamasima N 《Biochemical genetics》2001,39(7-8):251-260
Much is known about the antiviral activity of Mx proteins in species such as mouse and human. In the mouse, loss of resistibility to influenza virus has been shown to be due to specific polymorphisms in the Mx gene. This gene is therefore an interesting candidate gene for disease resistance in farm animals. The porcine Mx1 gene has already been identified and characterized based on its homology with mouse Mx1; however, until now no evidence of polymorphisms in the porcine gene has been reported. In this study, we have found two new polymorphisms in exon 14 of porcine Mx1 by DNA sequencing and confirmed their presence in different breeds, using polymerase chain reaction (PCR)–restriction fragment length polymorphisms (RFLP) with NarI and NaeI restriction enzymes. On the basis of the deduced amino acid sequence, one allele contains a deletion that may result in a frameshift to yield several amino acid substitutions and extension of the carboxyl terminal region of Mx1 protein. The deletion allele, Mx1
c, was found to be segregating in Landrace, Berkshire, Duroc, Hampshire, and Yucatan miniature pig. A second point mutation, Mx1
b, was detected in Meishan and two Vietnamese native pig breeds. All other breeds tested were fixed for the Mx1
a allele that is identical to the sequence reported previously. It will be interesting to determine if the Mx1
c deletion is associated with variation in resistance to the myxovirus family in the pig. 相似文献
59.
We investigated the photoperiodic response of serotonin- and galanin (GA)- immunoreactive (ir) cells in the paraventricular organ (PVO) and infundibular nucleus (IF) of the Japanese quail and the interaction of these cells with gonadotropin-releasing hormone (GnRH)-ir neurons in the hypothalamus. Serotonin-ir cells were located in series from the PVO to the IF, and were connected with each other. The number of serotonin-ir cells differed significantly between light and dark phases on the short days (SD), but did not differ between light and dark phases on long days (LD). GA-ir cells were also found in the PVO and IF. The number of GA-ir cells under SD conditions was significantly greater than under LD conditions but did not change diurnally. Both serotonin-ir and GA-ir fibers ran along the GnRH-ir cells in the nucleus commissurae pallii. Serotonin-ir and GA-ir fibers were connected with the GnRH-ir fibers in the external layer of the median eminence (ME). We confirmed that GA-ir fibers were closely associated with serotonin-ir neurons in the PVO and IF. GA-ir neurons have at least 2 routes of regulating GnRH neurons directly, and indirectly via the serotonin-ir cells in the PVO and IF. 相似文献
60.