全文获取类型
收费全文 | 687篇 |
免费 | 78篇 |
出版年
2022年 | 7篇 |
2021年 | 10篇 |
2018年 | 12篇 |
2017年 | 19篇 |
2016年 | 16篇 |
2015年 | 19篇 |
2014年 | 17篇 |
2013年 | 37篇 |
2012年 | 54篇 |
2011年 | 36篇 |
2010年 | 25篇 |
2009年 | 22篇 |
2008年 | 27篇 |
2007年 | 28篇 |
2006年 | 18篇 |
2005年 | 29篇 |
2004年 | 21篇 |
2003年 | 22篇 |
2002年 | 22篇 |
2001年 | 21篇 |
2000年 | 22篇 |
1999年 | 17篇 |
1998年 | 9篇 |
1996年 | 5篇 |
1995年 | 5篇 |
1993年 | 13篇 |
1992年 | 23篇 |
1991年 | 11篇 |
1990年 | 9篇 |
1989年 | 15篇 |
1988年 | 15篇 |
1987年 | 13篇 |
1986年 | 8篇 |
1985年 | 10篇 |
1984年 | 8篇 |
1983年 | 8篇 |
1982年 | 4篇 |
1981年 | 11篇 |
1980年 | 7篇 |
1979年 | 5篇 |
1978年 | 5篇 |
1977年 | 6篇 |
1976年 | 6篇 |
1975年 | 6篇 |
1974年 | 6篇 |
1973年 | 4篇 |
1972年 | 6篇 |
1970年 | 10篇 |
1969年 | 7篇 |
1967年 | 6篇 |
排序方式: 共有765条查询结果,搜索用时 281 毫秒
121.
Olivier Bezençon Luboš Remeň Sylvia Richard Catherine Roch Melanie Kessler Richard Moon Jacques Mawet Eric A. Ertel Thomas Pfeifer Bruno Capeleto 《Bioorganic & medicinal chemistry letters》2017,27(23):5322-5325
We identified and characterized a series of pyrazole amides as potent, selective Cav3.1-blockers. This series culminated with the identification of pyrazole amides 5a and 12d, with excellent potencies and/or selectivities toward the Cav3.2- and Cav3.3-channels. This compound displays poor DMPK properties, making its use difficult for in vivo applications. Nevertheless, this compound as well as analogous ones are well-suited for in vitro studies. 相似文献
122.
The ultimate and proximate mechanisms driving the evolution of long tails in forest deer mice 下载免费PDF全文
Evan P. Kingsley Krzysztof M. Kozak Susanne P. Pfeifer Dou‐Shuan Yang Hopi E. Hoekstra 《Evolution; international journal of organic evolution》2017,71(2):261-273
Understanding both the role of selection in driving phenotypic change and its underlying genetic basis remain major challenges in evolutionary biology. Here, we use modern tools to revisit a classic system of local adaptation in the North American deer mouse, Peromyscus maniculatus, which occupies two main habitat types: prairie and forest. Using historical collections, we find that forest‐dwelling mice have longer tails than those from nonforested habitat, even when we account for individual and population relatedness. Using genome‐wide SNP data, we show that mice from forested habitats in the eastern and western parts of their range form separate clades, suggesting that increased tail length evolved independently. We find that forest mice in the east and west have both more and longer caudal vertebrae, but not trunk vertebrae, than nearby prairie forms. By intercrossing prairie and forest mice, we show that the number and length of caudal vertebrae are not correlated in this recombinant population, indicating that variation in these traits is controlled by separate genetic loci. Together, these results demonstrate convergent evolution of the long‐tailed forest phenotype through two distinct genetic mechanisms, affecting number and length of vertebrae, and suggest that these morphological changes—either independently or together—are adaptive. 相似文献
123.
Nouha Ben-Othman Andhira Vieira Monica Courtney Fabien Record Elisabet Gjernes Fabio Avolio Biljana Hadzic Noémie Druelle Tiziana Napolitano Sergi Navarro-Sanz Serena Silvano Keith Al-Hasani Anja Pfeifer Sandra Lacas-Gervais Gunter Leuckx Laura Marroquí Julien Thévenet Ole Dragsbaek Madsen Patrick Collombat 《Cell》2017,168(1-2):73-85.e11
124.
Tyson E. Dietrich Carolyn J. Pfeifer Kelsey E. Aker Scott J. Bergman 《Current fungal infection reports》2017,11(1):5-15
Purpose of review
This article provides updates on antifungals, dosing strategies for safe and effective therapy in the critically ill, including special populations, and the understanding of resistance over the last 5 years.Recent findings
Reports of adverse effects with echinocandins have risen while antifungal resistance to this class has increased, especially in Candida glabrata. New formulations of posaconazole and isuvaconazole have been developed. Alternative dosing strategies including combination therapy are being evaluated for difficult to treat fungal infections. Other highlights include additional data on dosing patients with severe organ dysfunction, including those on continuous renal replacement therapy, and new breakpoints for individual Candida species being established for the echinocandins and triazole classes.Summary
Increasing resistance in Candida spp. has made susceptibility testing a standard of care for critically ill patients. New formulations of the triazole antifungals have made prevention and treatment of mold infections more of a reality. There are many implications that must be considered when treating critically ill patients due to alterations in pharmacokinetics and pharmacodynamics in order to ensure adequate treatment. This article exposes the need for further clinical research in treating invasive infections in this patient population.125.
Chromosomal engineering was used to localize the deoxyerythronolide B synthase (DEBS) genes and propionyl-CoA carboxylase (PCC) genes to the BAP1 Escherichia coli chromosome creating the new strain YW9. YW9 then featured a plasmid-free heterologous pathway for the production of the polyketide product 6-deoxyerythronolide B (6dEB, a precursor to the antibiotic erythromycin) highlighted by the successful chromosomal integration of five genes total and three DEBS genes each approximately 10 kb in length. The new strain was tested for small-scale 6dEB biosynthesis and compared to 6dEB production from plasmid-derived gene expression at 22, 30, and 37 degrees C. YW9 produced 6dEB at each temperature tested; whereas, the current plasmid-based system could only produce 6dEB at 22 and 30 degrees C. As determined by MS analysis, average production levels for YW9 were 0.47 (22 degrees C), 0.52 (30 degrees C), and 0.11 (37 degrees C)mg/L. 相似文献
126.
Ole Schulz-Trieglaff Nico Pfeifer Clemens Gröpl Oliver Kohlbacher Knut Reinert 《BMC bioinformatics》2008,9(1):423
Background
Mass Spectrometry coupled to Liquid Chromatography (LC-MS) is commonly used to analyze the protein content of biological samples in large scale studies. The data resulting from an LC-MS experiment is huge, highly complex and noisy. Accordingly, it has sparked new developments in Bioinformatics, especially in the fields of algorithm development, statistics and software engineering. In a quantitative label-free mass spectrometry experiment, crucial steps are the detection of peptide features in the mass spectra and the alignment of samples by correcting for shifts in retention time. At the moment, it is difficult to compare the plethora of algorithms for these tasks. So far, curated benchmark data exists only for peptide identification algorithms but no data that represents a ground truth for the evaluation of feature detection, alignment and filtering algorithms. 相似文献127.
128.
Ewerling S Hofmann A Klose R Weppert M Brem G Rink K Pfeifer A Wolf E 《Transgenic research》2006,15(4):447-454
Lentiviral transduction of oocytes or early embryos is an efficient strategy to generate transgenic rodents and livestock.
We evaluated laser-based microdrilling (MD) of the zona pellucida, which is a physical barrier for viral infection, and subsequent
incubation in virus suspension as a new route for lentiviral transgenesis in bovine. Lentiviral vectors carrying an eGFP expression
cassette were used to transduce oocytes or zygotes after MD as compared to the established subzonal virus injection technique
(MI). The type of manipulation (MD vs. MI) did not affect cleavage rates, but had a significant effect on blastocyst rates
(P < 0.001). MI of virus or sham-MI (buffer) resulted in higher blastocyst rates as compared to MD, both in the oocyte and zygote
treatment groups. The latter exhibited higher rates of early cleavage (P < 0.05) and blastocyst rates (P < 0.01). The proportion of eGFP expressing blastocysts was higher after infection of oocytes (MD: 44 ± 9%; MI: 67 ± 8%) than
after infection of zygotes (MD: 26 ± 8%; MI: 26 ± 9%). Overall efficacy (eGFP-positive blastocysts per treated oocytes or
zygotes) was highest after MI of oocytes (18 ± 2%). Our study demonstrates the feasibility of laser-assisted lentiviral gene
transfer into bovine oocytes and zygotes. However, further optimization of the procedure is required, mainly to reduce the
incidence of polyspermy after MD of oocytes and to eliminate negative effects of MD on early embryonic development.
S. Ewerling and A. Hofmann contributed equally 相似文献
129.
130.
Steffen Franz Mareva Ciatipis Kathrin Pfeifer Birthe Kierdorf Beatrice Sandner Ulrich Bogdahn Armin Blesch Beate Winner Norbert Weidner 《PloS one》2014,9(7)
After spinal cord injury, transected axons fail to regenerate, yet significant, spontaneous functional improvement can be observed over time. Distinct central nervous system regions retain the capacity to generate new neurons and glia from an endogenous pool of progenitor cells and to compensate neural cell loss following certain lesions. The aim of the present study was to investigate whether endogenous cell replacement (neurogenesis or gliogenesis) in the brain (subventricular zone, SVZ; corpus callosum, CC; hippocampus, HC; and motor cortex, MC) or cervical spinal cord might represent a structural correlate for spontaneous locomotor recovery after a thoracic spinal cord injury. Adult Fischer 344 rats received severe contusion injuries (200 kDyn) of the mid-thoracic spinal cord using an Infinite Horizon Impactor. Uninjured rats served as controls. From 4 to 14 days post-injury, both groups received injections of bromodeoxyuridine (BrdU) to label dividing cells. Over the course of six weeks post-injury, spontaneous recovery of locomotor function occurred. Survival of newly generated cells was unaltered in the SVZ, HC, CC, and the MC. Neurogenesis, as determined by identification and quantification of doublecortin immunoreactive neuroblasts or BrdU/neuronal nuclear antigen double positive newly generated neurons, was not present in non-neurogenic regions (MC, CC, and cervical spinal cord) and unaltered in neurogenic regions (dentate gyrus and SVZ) of the brain. The lack of neuronal replacement in the brain and spinal cord after spinal cord injury precludes any relevance for spontaneous recovery of locomotor function. Gliogenesis was increased in the cervical spinal cord remote from the injury site, however, is unlikely to contribute to functional improvement. 相似文献