全文获取类型
收费全文 | 8075篇 |
免费 | 747篇 |
国内免费 | 3篇 |
出版年
2023年 | 30篇 |
2022年 | 86篇 |
2021年 | 176篇 |
2020年 | 102篇 |
2019年 | 130篇 |
2018年 | 146篇 |
2017年 | 136篇 |
2016年 | 254篇 |
2015年 | 412篇 |
2014年 | 424篇 |
2013年 | 532篇 |
2012年 | 652篇 |
2011年 | 674篇 |
2010年 | 394篇 |
2009年 | 371篇 |
2008年 | 537篇 |
2007年 | 514篇 |
2006年 | 475篇 |
2005年 | 434篇 |
2004年 | 404篇 |
2003年 | 373篇 |
2002年 | 354篇 |
2001年 | 58篇 |
2000年 | 47篇 |
1999年 | 73篇 |
1998年 | 82篇 |
1997年 | 73篇 |
1996年 | 74篇 |
1995年 | 51篇 |
1994年 | 32篇 |
1993年 | 41篇 |
1992年 | 33篇 |
1991年 | 73篇 |
1990年 | 50篇 |
1989年 | 30篇 |
1988年 | 30篇 |
1987年 | 25篇 |
1986年 | 22篇 |
1985年 | 40篇 |
1984年 | 33篇 |
1983年 | 27篇 |
1982年 | 30篇 |
1981年 | 27篇 |
1980年 | 34篇 |
1979年 | 13篇 |
1977年 | 19篇 |
1976年 | 16篇 |
1975年 | 16篇 |
1974年 | 16篇 |
1973年 | 15篇 |
排序方式: 共有8825条查询结果,搜索用时 15 毫秒
91.
Elizabeth J. Fear Frida H. Torkelsen Elisa Zamboni Kuan-Ju Chen Martin Scott Glenn Jeffery Heidi Baseler Aneurin J. Kennerley 《Aging cell》2023,22(11):e14005
Mitochondrial function declines with age, and many pathological processes in neurodegenerative diseases stem from this dysfunction when mitochondria fail to produce the necessary energy required. Photobiomodulation (PBM), long-wavelength light therapy, has been shown to rescue mitochondrial function in animal models and improve human health, but clinical uptake is limited due to uncertainty around efficacy and the mechanisms responsible. Using 31P magnetisation transfer magnetic resonance spectroscopy (MT-MRS) we quantify, for the first time, the effects of 670 nm PBM treatment on healthy ageing human brains. We find a significant increase in the rate of ATP synthase flux in the brain after PBM in a cohort of older adults. Our study provides initial evidence of PBM therapeutic efficacy for improving mitochondrial function and restoring ATP flux with age, but recognises that wider studies are now required to confirm any resultant cognitive benefits. 相似文献
92.
Niraj Shrestha Pallavi Chaturvedi Xiaoyun Zhu Michael J. Dee Varghese George Christopher Janney Jack O. Egan Bai Liu Mark Foster Lynne Marsala Pamela Wong Celia C. Cubitt Jennifer A. Foltz Jennifer Tran Timothy Schappe Karin Hsiao Gilles M. Leclerc Lijing You Christian Echeverri Catherine Spanoudis Ana Carvalho Leah Kanakaraj Crystal Gilkes Nicole Encalada Lin Kong Meng Wang Byron Fang Zheng Wang Jin-an Jiao Gabriela J. Muniz Emily K. Jeng Nicole Valdivieso Liying Li Richard Deth Melissa M. Berrien-Elliott Todd A. Fehniger Peter R. Rhode Hing C. Wong 《Aging cell》2023,22(5):e13806
93.
Release of the cellular prion protein from cultured cells after loss of its glycoinositol phospholipid anchor 总被引:3,自引:0,他引:3
Borchelt David R.; Rogers Mark; Stahl Neil; Telling Glenn; Prusiner Stanley B. 《Glycobiology》1993,3(4):319-329
Secreted forms of the sialoglycoprotein designated cellularprion protein (PrPC) have been identified that cannot be explainedby alternative splicing. We report that secreted forms of PrPCderive from precursors that are bound to the plasma membraneby glycoinositol phospholipid (GPI) anchors. Secreted PrPC slowlyappeared in the culture medium of metabolically radiolabelledcells after incubations of 824 h. Digestion of nascentPrPC with phosphatidylinositol-specific phospholipase C (PIPLC)prevented the appearance of secreted PrPC. Secreted PrPc partitionedinto the aqueous phase of Triton X114 like PIPLC-releasedPrPC. While the Mr of PIPLC-released PrPC was reduced 24kDa after treatment with aqueous hydroflouric acid, which removesthe entire GPI anchor modification, the Mr of secreted PrPCwas unchanged. Both PIPLC-released and secreted PrPc were recognizedby antiserum raised against a synthetic C-terminal peptide correspondingto residues 220233 (amino acid 231 is the site of GPIattachment). We conclude that GPI-anchored PrPC is post-translationallyprocessed to remove most, if not all, of the GPI modificationand then shed into culture medium. Whether PrPC is shed afterproteolysis near the C-terminus remains to be established. Aminority of PrPC in normal Syrian hamster brain partitionedinto the aqueous phase of Triton X114 like shed PrPCsuggesting physiological significance. post-translational prion protein secretion sialoglycoprotein 相似文献
94.
Matthew D. Linnik Marsa D. Hatfield Melissa D. Swope Nahed K. Ahmed 《Developmental neurobiology》1993,24(4):433-446
Growth factor-dependent neurons die when they are deproved of their specific growth factor. This “programmed” cell death (PCD) requires macromolecular synthesis and is distinct from necrotic cell death. To investigate the mechanisms involved in neuronal PCD, we have studied the sequence of events that occur when a neuronal cell line (F-11: Mouse neuroblastoma X rat dorsal root ganglia) is deprived of serum in a manner analogous to growth factor deprivation from neurons. Protein synthesis was inhibited within the first 8 h of serum deprivation, while DNA cleavage into nucleosome ladders was prominent by 24 h. The DNA cleavage could be inhibited by cycloheximide, consistent with a requirement for protein synthesis. In contrast, mitochondrial function was not compromised by serum deprivation. Rather, the cells appeared to be metabolically activated after serum removal as shown by an increased reduction of MTT by mitochondrial dehydrogenases and an increase in cellular autofluorescence, which is thought to be due to elevated levels of NADH and flavoproteins. Assessment of cell viability by propidium iodide staining showed no indication of cell death within 24 h. After 48 h of serum deprivation, cells decreased in size and increased propidium iodide uptake. Thus, serum deprivation activates PCD in F-11 cells and may be a useful model to study the intracellular events responsible for PCD. © 1993 John Wiley & Sons, Inc. 相似文献
95.
The analysis of genomic data can be an intimidating process, particularly for researchers who are not experienced programmers. Commonly used analyses are spread across many programs, each requiring their own specific input formats, and so data must often be repeatedly reorganized and transformed into new formats. Analyses often require splitting data according to metadata variables such as population or family, which can be challenging to manage in large data sets. Here, we introduce snpR, a user-friendly data analysis package in R for processing SNP genomic data. snpR is designed to automate data subsetting and analyses across categorical metadata while also streamlining repeated analyses by integrating approaches contained in many different packages in a single ecosystem. snpR facilitates iterative and efficient analyses centred on a single R object for an entire analysis pipeline. 相似文献
96.
Wenping Li Melissa R. Pergande Christopher A. Crutchfield Brian C. Searle Peter S. Backlund Jaqueline A. Picache Kathryn Burkert Nicole M. Yanjanin-Farhat Paul S. Blank Cynthia L. Toth Christopher A. Wassif Forbes D. Porter Stephanie M. Cologna 《Proteomics》2023,23(11):2200378
Niemann-Pick, type C1 (NPC1) is a fatal, neurodegenerative disease, which belongs to the family of lysosomal diseases. In NPC1, endo/lysosomal accumulation of unesterified cholesterol and sphingolipids arise from improper intracellular trafficking resulting in multi-organ dysfunction. With the proximity between the brain and cerebrospinal fluid (CSF), performing differential proteomics provides a means to shed light to changes occurring in the brain. In this study, CSF samples obtained from NPC1 individuals and unaffected controls were used for protein biomarker identification. A subset of these individuals with NPC1 are being treated with miglustat, a glycosphingolipid synthesis inhibitor. Of the 300 identified proteins, 71 proteins were altered in individuals with NPC1 compared to controls including cathepsin D, and members of the complement family. Included are a report of 10 potential markers for monitoring therapeutic treatment. We observed that pro-neuropeptide Y (NPY) was significantly increased in NPC1 individuals relative to healthy controls; however, individuals treated with miglustat displayed levels comparable to healthy controls. In further investigation, NPY levels in a NPC1 mouse model corroborated our findings. We posit that NPY could be a potential therapeutic target for NPC1 due to its multiple roles in the central nervous system such as attenuating neuroinflammation and reducing excitotoxicity. 相似文献
97.
98.
Melissa Pederson Mussell Carol B. Peterson Christine L. Weller Ross D. Crosby Martina de Zwaan James E. Mitchell 《Obesity (Silver Spring, Md.)》1996,4(5):431-439
Obese individuals with binge eating disorder (BED) differ from obese non-binge eating (NBE) individuals in a number of clinically relevant ways. This study examined attitudinal responses to various measures of body image in women seeking obesity treatment, by comparing NBE participants (n=80) to those with BED (n=48). It was hypothesized that women with BED would demonstrate greater attitudinal disturbance of body image compared to NBE individuals. It was further hypothesized that significant differences between groups would remain after statistically controlling for degree of depression. Consistent with the primary hypothesis, BED participants reported significantly increased attitudinal disturbance in body dissatisfaction and size perception compared to NBE participants. Although shared variance was observed between measures of depression and body image on some items, several aspects of increased body image disturbance remained after statistically controlling for depression. Treatment implications and recommendations for future research are discussed. 相似文献
99.
We examined the effects of overexposure of testosterone (T) on fat cell morphology and adipocyte precursor pools in inguinal and retroperitoneal fat depots of ovariectomized rats. In both tissues peripubertal T decreased weights without affecting adipocyte mean cell size or the size distribution profiles, but adipocyte number was decreased by 65% in the inguinal and by 38% in the retroperitoneal depots. Immunofluorescent flow cytometry utilizing a specific antibody to rat adipose tissue lipoprotein lipase was used to quantify regional precursor cell populations. T sharply reduced the percentages of differentiated and undifferentiated preadipocytes in the inguinal depot, from 43.2 ± 5.3 to 23.5 ± 2.1% and from 57.7 ± 4.0 to 43.6 ± 5.3%, respectively, with a concomitant increase in fibroblasts from 1.6 to 32.9%. On the other hand, T had no effect on retroperitoneal preadipocyte pools. Perinatal andro-genization exacerbated the decline in the inguinal weight (1.4 ± 0.1 vs. 2.2 ± 0.1g) but otherwise did not influence the actions of peripubertal T. Androgens may thus act in a tissue-specific manner to regulate fat cell growth potential in the femoral region in the female. 相似文献
100.
Glenn L. Millhauser Chris J. Stenland Kimberly A. Bolin Frank J. M. van de Ven 《Journal of biomolecular NMR》1996,7(4):331-334
Summary Alanine-rich peptides serve as models for exploring the factors that control helix structure in peptides and proteins. Scalar CH-NH couplings (3JHN) are an extremely useful measure of local helix content; however, the large alanine content in these peptides leads to significant signal overlap in the CH region of 1H 2D NMR spectra. Quantitative determination of all possible 3JHN values is, therefore, very challenging. Szyperski and co-workers [(1992) J. Magn. Reson., 99, 552–560] have recently developed a method for determining 3JHN from NOESY spectra. Because 3JHN may be determined from 2D peaks outside of the CH region, there is a much greater likelihood of identifying resolved resonances and measuring the associated coupling constants. It is demonstrated here that 3JHN can be obtained for every residue in the helical peptide Ac-(AAAAK)3A-NH2. The resulting 3JHN profile clearly identifies a helical structure in the middle of the peptide and further suggests that the respective helix termini unfold via distinct pathways.Abbreviations
3JHN
three-bond CH-NH scalar coupling constant
- NOE
nuclear Overhauser enhancement
- NOESY
two-dimensional nuclear Overhauser spectroscopy
- COSY
two-dimensional correlated spectroscopy
- DQF-COSY
two-dimensional double-quantum-filtered correlated spectroscopy
- TOCSY
two-dimensional total correlation spectroscopy
To whom correspondence should be addressed.Deceased March 5, 1996. 相似文献