全文获取类型
收费全文 | 14529篇 |
免费 | 1404篇 |
国内免费 | 10篇 |
出版年
2023年 | 48篇 |
2021年 | 211篇 |
2020年 | 152篇 |
2019年 | 193篇 |
2018年 | 212篇 |
2017年 | 180篇 |
2016年 | 343篇 |
2015年 | 597篇 |
2014年 | 611篇 |
2013年 | 832篇 |
2012年 | 1000篇 |
2011年 | 1019篇 |
2010年 | 654篇 |
2009年 | 593篇 |
2008年 | 868篇 |
2007年 | 938篇 |
2006年 | 821篇 |
2005年 | 799篇 |
2004年 | 816篇 |
2003年 | 759篇 |
2002年 | 693篇 |
2001年 | 188篇 |
2000年 | 138篇 |
1999年 | 164篇 |
1998年 | 174篇 |
1997年 | 137篇 |
1996年 | 121篇 |
1995年 | 109篇 |
1994年 | 103篇 |
1993年 | 125篇 |
1992年 | 130篇 |
1991年 | 96篇 |
1990年 | 112篇 |
1989年 | 86篇 |
1988年 | 100篇 |
1987年 | 106篇 |
1986年 | 72篇 |
1985年 | 108篇 |
1984年 | 93篇 |
1983年 | 101篇 |
1982年 | 121篇 |
1981年 | 109篇 |
1980年 | 98篇 |
1979年 | 76篇 |
1978年 | 77篇 |
1977年 | 77篇 |
1976年 | 72篇 |
1975年 | 67篇 |
1974年 | 71篇 |
1973年 | 85篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
1.
2.
Anthony E. Kincaid Kathryn F. Hudson Matthew W. Richey Jason C. Bartz 《Journal of virology》2012,86(23):12731-12740
Prion infection and pathogenesis are dependent on the agent crossing an epithelial barrier to gain access to the recipient nervous system. Several routes of infection have been identified, but the mechanism(s) and timing of in vivo prion transport across an epithelium have not been determined. The hamster model of nasal cavity infection was used to determine the temporal and spatial parameters of prion-infected brain homogenate uptake following inhalation and to test the hypothesis that prions cross the nasal mucosa via M cells. A small drop of infected or uninfected brain homogenate was placed below each nostril, where it was immediately inhaled into the nasal cavity. Regularly spaced tissue sections through the entire extent of the nasal cavity were processed immunohistochemically to identify brain homogenate and the disease-associated isoform of the prion protein (PrPd). Infected or uninfected brain homogenate was identified adhering to M cells, passing between cells of the nasal mucosa, and within lymphatic vessels of the nasal cavity at all time points examined. PrPd was identified within a limited number of M cells 15 to 180 min following inoculation, but not in the adjacent nasal mucosa-associated lymphoid tissue (NALT). While these results support M cell transport of prions, larger amounts of infected brain homogenate were transported paracellularly across the respiratory, olfactory, and follicle-associated epithelia of the nasal cavity. These results indicate that prions can immediately cross the nasal mucosa via multiple routes and quickly enter lymphatics, where they can spread systemically via lymph draining the nasal cavity. 相似文献
3.
Mitchell P Rosen A Musa Zamah Shehua Shen Anthony T Dobson Charles E McCulloch Paolo F Rinaudo Julie D Lamb Marcelle I Cedars 《Reproductive biology and endocrinology : RB&E》2009,7(1):35-8
Background
Ovarian stimulation for assisted reproductive technology (ART) overcomes the physiologic process to develop a single dominant follicle. However, following stimulation, egg recovery rates are not 100%. The objective of this study is to determine if the follicular fluid hormonal environment is associated with oocyte recovery. 相似文献4.
5.
myc Boxes, Which Are Conserved in myc Family Proteins, Are Signals for Protein Degradation via the Proteasome 总被引:9,自引:4,他引:5 下载免费PDF全文
Elizabeth M. Flinn C. Magnus C. Busch Anthony P. H. Wright 《Molecular and cellular biology》1998,18(10):5961-5969
Cellular levels of the rapidly degraded c-myc protein play an important role in determining the proliferation status of cells. Increased levels of c-myc are frequently associated with rapidly proliferating tumor cells. We show here that myc boxes I and II, found in the N termini of all members of the myc protein family, function to direct the degradation of the c-myc protein. Both myc boxes I and II contain sufficient information to independently direct the degradation of otherwise stably expressed proteins to which they are fused. At least part of the myc box-directed degradation occurs via the proteasome. The mechanism of myc box-directed degradation appears to be conserved between yeast and mammalian cells. Our results suggest that the myc boxes may play an important role in regulating the level and activity of the c-myc protein. 相似文献
6.
7.
Anthony J. Hesketh Caroline Maloney Christopher A. Behr Morris C. Edelman Richard D. Glick Yousef Al-Abed Marc Symons Samuel Z. Soffer Bettie M. Steinberg 《PloS one》2015,10(12)
Metastatic Ewing Sarcoma carries a poor prognosis, and novel therapeutics to prevent and treat metastatic disease are greatly needed. Recent evidence demonstrates that tumor-associated macrophages in Ewing Sarcoma are associated with more advanced disease. While some macrophage phenotypes (M1) exhibit anti-tumor activity, distinct phenotypes (M2) may contribute to malignant progression and metastasis. In this study, we show that M2 macrophages promote Ewing Sarcoma invasion and extravasation, pointing to a potential target of anti-metastatic therapy. CNI-1493 is a selective inhibitor of macrophage function and has shown to be safe in clinical trials as an anti-inflammatory agent. In a xenograft mouse model of metastatic Ewing Sarcoma, CNI-1493 treatment dramatically reduces metastatic tumor burden. Furthermore, metastases in treated animals have a less invasive morphology. We show in vitro that CNI-1493 decreases M2-stimulated Ewing Sarcoma tumor cell invasion and extravasation, offering a functional mechanism through which CNI-1493 attenuates metastasis. These data indicate that CNI-1493 may be a safe and effective adjuvant agent for the prevention and treatment of metastatic Ewing Sarcoma. 相似文献
8.
9.
Harriet M. Jackson Kristen D. Onos Keating W. Pepper Leah C. Graham Ellen C. Akeson Candice Byers Laura G. Reinholdt Wayne N. Frankel Gareth R. Howell 《PloS one》2015,10(5)
Alzheimer’s disease (AD) is a leading cause of dementia in the elderly and is characterized by amyloid plaques, neurofibrillary tangles (NFTs) and neuronal dysfunction. Early onset AD (EOAD) is commonly caused by mutations in amyloid precursor protein (APP) or genes involved in the processing of APP including the presenilins (e.g. PSEN1 or PSEN2). In general, mouse models relevant to EOAD recapitulate amyloidosis, show only limited amounts of NFTs and neuronal cell dysfunction and low but significant levels of seizure susceptibility. To investigate the effect of genetic background on these phenotypes, we generated APPswe and PSEN1de9 transgenic mice on the seizure prone inbred strain background, DBA/2J. Previous studies show that the DBA/2J genetic background modifies plaque deposition in the presence of mutant APP but the impact of PSEN1de9 has not been tested. Our study shows that DBA/2J.APPswePSEN1de9 mice are significantly more prone to premature lethality, likely to due to lethal seizures, compared to B6.APPswePSEN1de9 mice—70% of DBA/2J.APPswePSEN1de9 mice die between 2-3 months of age. Of the DBA/2J.APPswePSEN1de9 mice that survived to 6 months of age, plaque deposition was greatly reduced compared to age-matched B6.APPswePSEN1de9 mice. The reduction in plaque deposition appears to be independent of microglia numbers, reactive astrocytosis and complement C5 activity. 相似文献
10.