全文获取类型
收费全文 | 363篇 |
免费 | 51篇 |
出版年
2022年 | 2篇 |
2021年 | 2篇 |
2020年 | 4篇 |
2019年 | 9篇 |
2018年 | 2篇 |
2017年 | 3篇 |
2016年 | 4篇 |
2015年 | 11篇 |
2014年 | 6篇 |
2013年 | 28篇 |
2012年 | 10篇 |
2011年 | 22篇 |
2010年 | 11篇 |
2009年 | 13篇 |
2008年 | 12篇 |
2007年 | 15篇 |
2006年 | 12篇 |
2005年 | 15篇 |
2004年 | 20篇 |
2003年 | 22篇 |
2002年 | 9篇 |
2001年 | 10篇 |
2000年 | 14篇 |
1999年 | 11篇 |
1998年 | 8篇 |
1997年 | 5篇 |
1996年 | 3篇 |
1995年 | 3篇 |
1994年 | 7篇 |
1993年 | 4篇 |
1992年 | 10篇 |
1991年 | 14篇 |
1990年 | 4篇 |
1988年 | 7篇 |
1987年 | 4篇 |
1986年 | 2篇 |
1985年 | 5篇 |
1984年 | 5篇 |
1983年 | 6篇 |
1981年 | 3篇 |
1979年 | 8篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1975年 | 11篇 |
1974年 | 3篇 |
1973年 | 4篇 |
1972年 | 5篇 |
1971年 | 5篇 |
1970年 | 5篇 |
1969年 | 5篇 |
排序方式: 共有414条查询结果,搜索用时 156 毫秒
31.
32.
Lombard DB Beard C Johnson B Marciniak RA Dausman J Bronson R Buhlmann JE Lipman R Curry R Sharpe A Jaenisch R Guarente L 《Molecular and cellular biology》2000,20(9):3286-3291
Werner's syndrome (WS) is a human disease with manifestations resembling premature aging. The gene defective in WS, WRN, encodes a DNA helicase. Here, we describe the generation of mice bearing a mutation that eliminates expression of the C terminus of the helicase domain of the WRN protein. Mutant mice are born at the expected Mendelian frequency and do not show any overt histological signs of accelerated senescence. These mice are capable of living beyond 2 years of age. Cells from these animals do not show elevated susceptibility to the genotoxins camptothecin or 4-NQO. However, mutant fibroblasts senesce approximately one passage earlier than controls. Importantly, WRN(-/-);p53(-/-) mice show an increased mortality rate relative to WRN(+/-);p53(-/-) animals. We consider possible models for the synergy between p53 and WRN mutations for the determination of life span. 相似文献
33.
34.
Raimon Duran-Struuck Christene A Huang Katherine Orf Roderick T Bronson David H Sachs Thomas R Spitzer 《Comparative medicine》2015,65(5):429-443
Miniature swine provide a preclinical model of hematopoietic cell transplantation (HCT) for studies of graft-versus-host disease. HCT between MHC-matched or ‑mismatched pigs can be performed to mimic clinical scenarios with outcomes that closely resemble those observed in human HCT recipients. With myeloablative conditioning, HCT across MHC barriers is typically fatal, with pigs developing severe (grade III or IV) GVHD involving the gastrointestinal tract, liver, and skin. Unlike rodent models, miniature swine provide an opportunity to perform extended longitudinal studies on individual animals, because multiple tissue biopsies can be harvested without the need for euthanasia. In addition, we have developed a swine GVHD scoring system that parallels that used in the human clinical setting. Given the similarities of GVHD in pigs and humans, we hope that the use of this scoring system facilitates clinical and scientific discourse between the laboratory and the clinic. We anticipate that results of swine studies will support the development of new strategies to improve the identification and treatment of GVHD in clinical HCT scenarios.Abbreviations: BMT, bone marrow transplantation; GVHD, graft-versus-host disease; GVL, graft-versus-leukemia; HCT, hematopoietic cell transplantation; TBI, total-body irradiation 相似文献
35.
GUILLAUME TCHERKEZ RUDI SCHÄUFELE SALVADOR NOGUÉS CLÉMENT PIEL ARNOUD BOOM GARY LANIGAN CÉCILE BARBAROUX CATARINA MATA SLIMAN ELHANI DEBBIE HEMMING CHRISTINA MAGUAS DAN YAKIR FRANZ W. BADECK HOWARD GRIFFITHS HANS SCHNYDER JALEH GHASHGHAIE 《Plant, cell & environment》2010,33(6):900-913
While there is currently intense effort to examine the 13C signal of CO2 evolved in the dark, less is known on the isotope composition of day‐respired CO2. This lack of knowledge stems from technical difficulties to measure the pure respiratory isotopic signal: day respiration is mixed up with photorespiration, and there is no obvious way to separate photosynthetic fractionation (pure ci/ca effect) from respiratory effect (production of CO2 with a different δ13C value from that of net‐fixed CO2) at the ecosystem level. Here, we took advantage of new simple equations, and applied them to sunflower canopies grown under low and high [CO2]. We show that whole mesocosm‐respired CO2 is slightly 13C depleted in the light at the mesocosm level (by 0.2–0.8‰), while it is slightly 13C enriched in darkness (by 1.5–3.2‰). The turnover of the respiratory carbon pool after labelling appears similar in the light and in the dark, and accordingly, a hierarchical clustering analysis shows a close correlation between the 13C abundance in day‐ and night‐evolved CO2. We conclude that the carbon source for respiration is similar in the dark and in the light, but the metabolic pathways associated with CO2 production may change, thereby explaining the different 12C/13C respiratory fractionations in the light and in the dark. 相似文献
36.
37.
Parker MF Bronson JJ Barten DM Corsa JA Du W Felsenstein KM Guss VL Izzarelli D Loo A McElhone KE Marcin LR Padmanabha R Pak R Polson CT Toyn JH Varma S Wang J Wong V Zheng M Roberts SB 《Bioorganic & medicinal chemistry letters》2007,17(21):5790-5795
A series of amino-caprolactam sulfonamides were developed from a screening hit. Compounds with good in vitro and in vivo gamma-secretase activity are reported. 相似文献
38.
Parker MF Barten DM Bergstrom CP Bronson JJ Corsa JA Deshpande MS Felsenstein KM Guss VL Hansel SB Johnson G Keavy DJ Lau WY Mock J Prasad CV Polson CT Sloan CP Smith DW Wallace OB Wang HH Williams A Zheng M 《Bioorganic & medicinal chemistry letters》2007,17(16):4432-4436
A series of N-alkylbenzenesulfonamides were developed from a high throughput screening hit. Classic and parallel synthesis strategies were employed to produce compounds with good in vitro and in vivo gamma-secretase activity. 相似文献
39.
MORAIS PAULO AMORIM ANTÓNIO VIEIRA DA SILVA CLÁUDIA RIBEIRO TERESA COSTA SANTOS JORGE AFONSO COSTA HELOÍSA 《Journal of genetics》2015,94(3):509-512
Journal of Genetics - 相似文献
40.
Boy KM Guernon JM Shi J Toyn JH Meredith JE Barten DM Burton CR Albright CF Marcinkeviciene J Good AC Tebben AJ Muckelbauer JK Camac DM Lentz KA Bronson JJ Olson RE Macor JE Thompson LA 《Bioorganic & medicinal chemistry letters》2011,21(22):6916-6924
The synthesis, evaluation, and structure-activity relationships of a class of γ-lactam 1,3-diaminopropan-2-ol transition-state isostere inhibitors of BACE are discussed. Two strategies for optimizing lead compound 1a are presented. Reducing the overall size of the inhibitors resulted in the identification of γ-lactam 1i, whereas the introduction of conformational constraint on the prime-side of the inhibitor generated compounds such as the 3-hydroxypyrrolidine inhibitor 28n. The full in vivo profile of 1i in rats and 28n in Tg 2576 mice is presented. 相似文献