全文获取类型
收费全文 | 6414篇 |
免费 | 542篇 |
国内免费 | 5篇 |
出版年
2023年 | 34篇 |
2022年 | 98篇 |
2021年 | 176篇 |
2020年 | 90篇 |
2019年 | 98篇 |
2018年 | 138篇 |
2017年 | 128篇 |
2016年 | 222篇 |
2015年 | 402篇 |
2014年 | 443篇 |
2013年 | 434篇 |
2012年 | 631篇 |
2011年 | 575篇 |
2010年 | 338篇 |
2009年 | 295篇 |
2008年 | 408篇 |
2007年 | 405篇 |
2006年 | 387篇 |
2005年 | 294篇 |
2004年 | 317篇 |
2003年 | 213篇 |
2002年 | 229篇 |
2001年 | 47篇 |
2000年 | 34篇 |
1999年 | 55篇 |
1998年 | 43篇 |
1997年 | 45篇 |
1996年 | 29篇 |
1995年 | 21篇 |
1994年 | 38篇 |
1993年 | 22篇 |
1992年 | 26篇 |
1991年 | 22篇 |
1990年 | 14篇 |
1989年 | 15篇 |
1988年 | 9篇 |
1987年 | 10篇 |
1986年 | 12篇 |
1985年 | 12篇 |
1984年 | 13篇 |
1983年 | 17篇 |
1982年 | 7篇 |
1981年 | 9篇 |
1980年 | 15篇 |
1979年 | 8篇 |
1978年 | 9篇 |
1977年 | 19篇 |
1975年 | 5篇 |
1974年 | 8篇 |
1973年 | 8篇 |
排序方式: 共有6961条查询结果,搜索用时 15 毫秒
71.
72.
Evelyn L. Jensen Christina Tschritter Peter V. C. de Groot Kristen M. Hayward Marsha Branigan Markus Dyck Rute B. G. Clemente‐Carvalho Stephen C. Lougheed 《Ecology and evolution》2020,10(8):3706-3714
Predicting the consequences of environmental changes, including human‐mediated climate change on species, requires that we quantify range‐wide patterns of genetic diversity and identify the ecological, environmental, and historical factors that have contributed to it. Here, we generate baseline data on polar bear population structure across most Canadian subpopulations (n = 358) using 13,488 genome‐wide single nucleotide polymorphisms (SNPs) identified with double‐digest restriction site‐associated DNA sequencing (ddRAD). Our ddRAD dataset showed three genetic clusters in the sampled Canadian range, congruent with previous studies based on microsatellites across the same regions; however, due to a lack of sampling in Norwegian Bay, we were unable to confirm the existence of a unique cluster in that subpopulation. These data on the genetic structure of polar bears using SNPs provide a detailed baseline against which future shifts in population structure can be assessed, and opportunities to develop new noninvasive tools for monitoring polar bears across their range. 相似文献
73.
74.
75.
76.
77.
78.
Birthe Tegtmeyer Gabrielle Vieyres Daniel Todt Chris Lauber Corinne Ginkel Michael Engelmann Maike Herrmann Christian K. Pfaller Florian W. R. Vondran Ruth Broering Ehsan Vafadarnejad Antoine-Emmanuel Saliba Christina Puff Wolfgang Baumgrtner Csaba Miskey Zoltn Ivics Eike Steinmann Thomas Pietschmann Richard J. P. Brown 《Journal of virology》2021,95(10)
79.
Joost Groot Yizhou Zhou Eric Marshall Patrick Cullen Thomas Carlile Dongdong Lin Chong-Feng Xu Justin Crisafulli Chao Sun Fergal Casey Baohong Zhang Christina Alves 《Biotechnology journal》2021,16(8):2000548
In recent years, High-Throughput Sequencing (HTS) based methods to detect mutations in biotherapeutic transgene products have become a key quality step deployed during the development of manufacturing cell line clones. Previously we reported on a higher throughput, rapid mutation detection method based on amplicon sequencing (targeting transgene RNA) and detailed its implementation to facilitate cell line clone selection. By gaining experience with our assay in a diverse set of cell line development programs, we improved the computational analysis as well as experimental protocols. Here we report on these improvements as well as on a comprehensive benchmarking of our assay. We evaluated assay performance by mixing amplicon samples of a verified mutated antibody clone with a non-mutated antibody clone to generate spike-in mutations from ∼60% down to ∼0.3% frequencies. We subsequently tested the effect of 16 different sample and HTS library preparation protocols on the assay's ability to quantify mutations and on the occurrence of false-positive background error mutations (artifacts). Our evaluation confirmed assay robustness, established a high confidence limit of detection of ∼0.6%, and identified protocols that reduce error levels thereby significantly reducing a source of false positives that bottlenecked the identification of low-level true mutations. 相似文献
80.
Tarah A. Word Ann P. Quick Christina Y. Miyake Mayra K. Shak Xiaolu Pan Jean J. Kim Hugh D. Allen Martha Sibrian-Vazquez Robert M. Strongin Andrew P. Landstrom Xander H. T. Wehrens 《Journal of cellular and molecular medicine》2021,25(13):6115-6124
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited cardiac arrhythmia syndrome that often leads to sudden cardiac death. The most common form of CPVT is caused by autosomal-dominant variants in the cardiac ryanodine receptor type-2 (RYR2) gene. Mutations in RYR2 promote calcium (Ca2+) leak from the sarcoplasmic reticulum (SR), triggering lethal arrhythmias. Recently, it was demonstrated that tetracaine derivative EL20 specifically inhibits mutant RyR2, normalizes Ca2+ handling and suppresses arrhythmias in a CPVT mouse model. The objective of this study was to determine whether EL20 normalizes SR Ca2+ handling and arrhythmic events in induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) from a CPVT patient. Blood samples from a child carrying RyR2 variant RyR2 variant Arg-176-Glu (R176Q) and a mutation-negative relative were reprogrammed into iPSCs using a Sendai virus system. iPSC-CMs were derived using the StemdiffTM kit. Confocal Ca2+ imaging was used to quantify RyR2 activity in the absence and presence of EL20. iPSC-CMs harbouring the R176Q variant demonstrated spontaneous SR Ca2+ release events, whereas administration of EL20 diminished these abnormal events at low nanomolar concentrations (IC50 = 82 nM). Importantly, treatment with EL20 did not have any adverse effects on systolic Ca2+ handling in control iPSC-CMs. Our results show for the first time that tetracaine derivative EL20 normalized SR Ca2+ handling and suppresses arrhythmogenic activity in iPSC-CMs derived from a CPVT patient. Hence, this study confirms that this RyR2-inhibitor represents a promising therapeutic candidate for treatment of CPVT. 相似文献