全文获取类型
收费全文 | 10076篇 |
免费 | 934篇 |
专业分类
11010篇 |
出版年
2024年 | 3篇 |
2023年 | 57篇 |
2022年 | 137篇 |
2021年 | 281篇 |
2020年 | 136篇 |
2019年 | 188篇 |
2018年 | 236篇 |
2017年 | 195篇 |
2016年 | 307篇 |
2015年 | 538篇 |
2014年 | 596篇 |
2013年 | 643篇 |
2012年 | 1000篇 |
2011年 | 992篇 |
2010年 | 578篇 |
2009年 | 499篇 |
2008年 | 764篇 |
2007年 | 735篇 |
2006年 | 661篇 |
2005年 | 589篇 |
2004年 | 541篇 |
2003年 | 489篇 |
2002年 | 424篇 |
2001年 | 86篇 |
2000年 | 39篇 |
1999年 | 49篇 |
1998年 | 65篇 |
1997年 | 44篇 |
1996年 | 17篇 |
1995年 | 17篇 |
1994年 | 11篇 |
1993年 | 12篇 |
1992年 | 6篇 |
1991年 | 4篇 |
1990年 | 6篇 |
1987年 | 4篇 |
1986年 | 3篇 |
1983年 | 4篇 |
1982年 | 7篇 |
1981年 | 5篇 |
1979年 | 3篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1972年 | 5篇 |
1969年 | 2篇 |
1968年 | 3篇 |
1965年 | 2篇 |
1954年 | 2篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
51.
Multiple targets of miR-302 and miR-372 promote reprogramming of human fibroblasts to induced pluripotent stem cells 总被引:1,自引:0,他引:1
Subramanyam D Lamouille S Judson RL Liu JY Bucay N Derynck R Blelloch R 《Nature biotechnology》2011,29(5):443-448
The embryonic stem cell-specific cell cycle-regulating (ESCC) family of microRNAs (miRNAs) enhances reprogramming of mouse embryonic fibroblasts to induced pluripotent stem cells. Here we show that the human ESCC miRNA orthologs hsa-miR-302b and hsa-miR-372 promote human somatic cell reprogramming. Furthermore, these miRNAs repress multiple target genes, with downregulation of individual targets only partially recapitulating the total miRNA effects. These targets regulate various cellular processes, including cell cycle, epithelial-mesenchymal transition (EMT), epigenetic regulation and vesicular transport. ESCC miRNAs have a known role in regulating the unique embryonic stem cell cycle. We show that they also increase the kinetics of mesenchymal-epithelial transition during reprogramming and block TGFβ-induced EMT of human epithelial cells. These results demonstrate that the ESCC miRNAs promote dedifferentiation by acting on multiple downstream pathways. We propose that individual miRNAs generally act through numerous pathways that synergize to regulate and enforce cell fate decisions. 相似文献
52.
A comparison of chemical pretreatment methods for improving saccharification of cotton stalks 总被引:19,自引:0,他引:19
Silverstein RA Chen Y Sharma-Shivappa RR Boyette MD Osborne J 《Bioresource technology》2007,98(16):3000-3011
The effectiveness of sulfuric acid (H(2)SO(4)), sodium hydroxide (NaOH), hydrogen peroxide (H(2)O(2)), and ozone pretreatments for conversion of cotton stalks to ethanol was investigated. Ground cotton stalks at a solid loading of 10% (w/v) were pretreated with H(2)SO(4), NaOH, and H(2)O(2) at concentrations of 0.5%, 1%, and 2% (w/v). Treatment temperatures of 90 degrees C and 121 degrees C at 15 psi were investigated for residence times of 30, 60, and 90 min. Ozone pretreatment was performed at 4 degrees C with constant sparging of stalks in water. Solids from H(2)SO(4), NaOH, and H(2)O(2) pretreatments (at 2%, 60 min, 121 degrees C/15 psi) showed significant lignin degradation and/or high sugar availability and hence were hydrolyzed by Celluclast 1.5L and Novozym 188 at 50 degrees C. Sulfuric acid pretreatment resulted in the highest xylan reduction (95.23% for 2% acid, 90 min, 121 degrees C/15 psi) but the lowest cellulose to glucose conversion during hydrolysis (23.85%). Sodium hydroxide pretreatment resulted in the highest level of delignification (65.63% for 2% NaOH, 90 min, 121 degrees C/15 psi) and cellulose conversion (60.8%). Hydrogen peroxide pretreatment resulted in significantly lower (p相似文献
53.
The genetic material, deoxyribonucleic acid (DNA), contains information about the evolutionary history of life. Both the relationships
amongst organisms and the times of their divergence can be inferred from DNA sequences. Anthropological geneticists use DNA
sequences to infer the evolutionary history of humans and their primate relatives. We review the basic methodology used to
infer these relationships. We then review the anthropological genetic evidence for modern human origins. We conclude that
modern humans evolved recently in Africa and then left to colonize the rest of the world within the last 50,000 years, largely
replacing the other human groups that they encountered. Modern humans likely exchanged genes with Neanderthals prior to or
early during their expansion out of Africa. 相似文献
54.
55.
56.
Genetic mouse models are an important tool in the study of mammalian neural tube closure (Gray & Ross, 2009; Ross, 2010). However, the study of mouse embryos in utero is limited by our inability to directly pharmacologically manipulate the embryos in isolation from the effects of maternal metabolism on the reagent of interest. Whether using a small molecule, recombinant protein, or siRNA, delivery of these substances to the mother, through the diet or by injection will subject these unstable compounds to a variety of bodily defenses that could prevent them from reaching the embryo. Investigations in cultures of whole embryos can be used to separate maternal from intrinsic fetal effects on development.Here, we present a method for culturing mouse embryos using highly enriched media in a roller incubator apparatus that allows for normal neural tube closure after dissection (Crockett, 1990). Once in culture, embryos can be manipulated using conventional in vitro techniques that would not otherwise be possible if the embryos were still in utero. Embryo siblings can be collected at various time points to study different aspects of neurulation, occurring from E7-7.5 (neural plate formation, just prior to the initiation of neurulation) to E9.5-10 (at the conclusion of cranial fold and caudal neuropore closure, Kaufman, 1992). In this protocol, we demonstrate our method for dissecting embryos at timepoints that are optimal for the study of cranial neurulation. Embryos will be dissected at E8.5 (approx. 10-12 somities), after the initiation of neural tube closure but prior to embryo turning and cranial neural fold closure, and maintained in culture till E10 (26-28 somities), when cranial neurulation should be complete. 相似文献
57.
Recruitment and derecruitment (R/D) of air spaces within the lung is greatly enhanced in lung injury and is thought to be responsible for exacerbating injury during mechanical ventilation. There is evidence to suggest that R/D is a time-dependent phenomenon. We have developed a computer model of the lung consisting of a parallel arrangement of airways and alveolar units. Each airway has a critical pressure (Pcrit) above which it tends to open and below which it tends to close but at a rate determined by how far pressure is from Pcrit. With an appropriate distribution of Pcrit and R/D velocity characteristics, the model able to produce realistic first and second pressure-volume curves of a lung inflated from an initially degassed state. The model also predicts that lung elastance will increase transiently after a deep inflation to a degree that increases as lung volume decreases and as the lung becomes injured. We conclude that our model captures the time-dependent mechanical behavior of the lung due to gradual R/D of lung units. 相似文献
58.
Differential Effects of AGS3 Expression on D2L
Dopamine Receptor-Mediated Adenylyl Cyclase Signaling
Activator of G protein signaling 3 (AGS3) binds Gαi subunits in the GDP-bound state, implicating AGS3 as an important regulator of Gαi-linked receptor (e.g., D2 dopamine and μ-opioid) signaling. We examined the ability of AGS3 to modulate recombinant adenylyl cyclase (AC) type 1 and 2 signaling in HEK293 cells following both acute and persistent activation of the D2L dopamine receptor (D2LDR). AGS3 expression modestly enhanced the potency of acute quinpirole-induced D2LDR modulation of AC1 or AC2 activity. AGS3 also promoted desensitization of D2LDR-mediated inhibition of AC1, whereas desensitization of D2LDR-mediated AC2 activation was significantly attenuated. Additionally, AGS3 reduced D2LDR-mediated sensitization of AC1 and AC2. These data suggest that AGS3 is involved in altering G protein signaling in a complex fashion that is effector-specific and dependent on the duration of receptor activation. 相似文献
59.
Changes in vegetation patterns on the margins of a constructed wetland after 10 years 总被引:4,自引:0,他引:4
Summary A constructed urban wetland in Adelaide was surveyed 18 months and 10 years after construction to see how shoreline vegetation, soil electrical conductivity (EC), texture and pH changed over time and to provide data for future site management. Multivariate analysis detected four plant associations at 18 months: salt‐tolerant taxa on conductive clays; a weed‐dominated community on lower EC soil; and two smaller waterlogged, low EC clusters dominated by Common Reed (Phragmites australis) and Sea Club‐Rush (Bolboschoenus caldwellii), respectively. At 10 years, site cover and heterogeneity was higher, with the margins dominated by Phragmites and salt‐tolerant species. EC was much lower and more uniform, and the soils were heavier and more alkaline. Managed storm water flushing apparently lowered soil EC, but possibly also disturbed the shoreline. However, weeds were still common, and the potential for domination by Phragmites at the expense of other native shoreline species means that ongoing monitoring and hydrological and vegetation management are essential to maintain site habitat diversity. 相似文献
60.
Xiuhua Li Laney Redus Cang Chen Paul A. Martinez Randy Strong Senlin Li Jason C. O’Connor 《PloS one》2013,8(8)
Parkinson’s disease (PD) is a neurodegenerative disorder primarily characterized by progressive loss of dopamine neurons, leading to loss of motor coordination. However, PD is associated with a high rate of non-motor neuropsychiatric comorbities that often develop before the onset of movement symptoms. The MitoPark transgenic mouse model is the first to recapitulate the cardinal clinical features, namely progressive neurodegeneration and death of neurons, loss of motor function and therapeutic response to L-DOPA. To investigate whether MitoPark mice exhibit early onset of cognitive impairment, a non-motor neuropsychiatric comorbidity, we measured performance on a spatial learning and memory task before (∼8 weeks) or after (∼20 weeks) the onset of locomotor decline in MitoPark mice or in littermate controls. Consistent with previous studies, we established that a progressive loss of spontaneous locomotor activity began at 12 weeks of age, which was followed by progressive loss of body weight beginning at 16–20 weeks. Spatial learning and memory was measured using the Barnes Maze. By 20 weeks of age, MitoPark mice displayed a substantial reduction in overall locomotor activity that impaired their ability to perform the task. However, in the 8-week-old mice, locomotor activity was no different between genotypes, yet MitoPark mice took longer, traveled further and committed more errors than same age control mice, while learning to successfully navigate the maze. The modest between-day learning deficit of MitoPark mice was characterized by impaired within-day learning during the first two days of testing. No difference was observed between genotypes during probe trials conducted one or twelve days after the final acquisition test. Additionally, 8-week-old MitoPark mice exhibited impaired novel object recognition when compared to control mice. Together, these data establish that mild cognitive impairment precedes the loss of motor function in a novel rodent model of PD, which may provide unique opportunities for therapeutic development. 相似文献