全文获取类型
收费全文 | 2350篇 |
免费 | 200篇 |
出版年
2022年 | 24篇 |
2021年 | 59篇 |
2020年 | 37篇 |
2019年 | 37篇 |
2018年 | 37篇 |
2017年 | 34篇 |
2016年 | 49篇 |
2015年 | 112篇 |
2014年 | 110篇 |
2013年 | 121篇 |
2012年 | 128篇 |
2011年 | 156篇 |
2010年 | 102篇 |
2009年 | 93篇 |
2008年 | 102篇 |
2007年 | 137篇 |
2006年 | 97篇 |
2005年 | 94篇 |
2004年 | 83篇 |
2003年 | 82篇 |
2002年 | 71篇 |
2001年 | 36篇 |
2000年 | 27篇 |
1999年 | 19篇 |
1998年 | 30篇 |
1997年 | 26篇 |
1996年 | 16篇 |
1995年 | 21篇 |
1994年 | 12篇 |
1993年 | 11篇 |
1992年 | 13篇 |
1991年 | 16篇 |
1990年 | 17篇 |
1989年 | 19篇 |
1988年 | 18篇 |
1986年 | 16篇 |
1985年 | 11篇 |
1984年 | 17篇 |
1983年 | 18篇 |
1982年 | 34篇 |
1981年 | 15篇 |
1980年 | 10篇 |
1979年 | 13篇 |
1978年 | 17篇 |
1977年 | 16篇 |
1976年 | 21篇 |
1974年 | 15篇 |
1968年 | 11篇 |
1964年 | 14篇 |
1962年 | 11篇 |
排序方式: 共有2550条查询结果,搜索用时 448 毫秒
201.
Ágnes Baross Allen D Delaney H Irene Li Tarun Nayar Stephane Flibotte Hong Qian Susanna Y Chan Jennifer Asano Adrian Ally Manqiu Cao Patricia Birch Mabel Brown-John Nicole Fernandes Anne Go Giulia Kennedy Sylvie Langlois Patrice Eydoux JM Friedman Marco A Marra 《BMC bioinformatics》2007,8(1):1-18
Background
Genomic deletions and duplications are important in the pathogenesis of diseases, such as cancer and mental retardation, and have recently been shown to occur frequently in unaffected individuals as polymorphisms. Affymetrix GeneChip whole genome sampling analysis (WGSA) combined with 100 K single nucleotide polymorphism (SNP) genotyping arrays is one of several microarray-based approaches that are now being used to detect such structural genomic changes. The popularity of this technology and its associated open source data format have resulted in the development of an increasing number of software packages for the analysis of copy number changes using these SNP arrays.Results
We evaluated four publicly available software packages for high throughput copy number analysis using synthetic and empirical 100 K SNP array data sets, the latter obtained from 107 mental retardation (MR) patients and their unaffected parents and siblings. We evaluated the software with regards to overall suitability for high-throughput 100 K SNP array data analysis, as well as effectiveness of normalization, scaling with various reference sets and feature extraction, as well as true and false positive rates of genomic copy number variant (CNV) detection.Conclusion
We observed considerable variation among the numbers and types of candidate CNVs detected by different analysis approaches, and found that multiple programs were needed to find all real aberrations in our test set. The frequency of false positive deletions was substantial, but could be greatly reduced by using the SNP genotype information to confirm loss of heterozygosity. 相似文献202.
Schilders G Raijmakers R Malmegrim KC Vande Walle L Saelens X Vree Egberts W van Venrooij WJ Vandenabeele P Pruijn GJ 《Arthritis research & therapy》2007,9(1):R12
Recent studies have implicated the dying cell as a potential reservoir of modified autoantigens that might initiate and drive
systemic autoimmunity in susceptible hosts. A number of subunits of the exosome, a complex of 3'→5' exoribonucleases that
functions in a variety of cellular processes, are recognized by the so-called anti-PM/Scl autoantibodies, found predominantly
in patients suffering from an overlap syndrome of myositis and scleroderma. Here we show that one of these subunits, PM/Scl-75,
is cleaved during apoptosis. PM/Scl-75 cleavage is inhibited by several different caspase inhibitors. The analysis of PM/Scl-75
cleavage by recombinant caspase proteins shows that PM/Scl-75 is efficiently cleaved by caspase-1, to a smaller extent by
caspase-8, and relatively inefficiently by caspase-3 and caspase-7. Cleavage of the PM/Scl-75 protein occurs in the C-terminal
part of the protein at Asp369 (IILD369↓G), and at least a fraction of the resulting N-terminal fragments of PM/Scl-75 remains associated with the exosome. Finally,
the implications of PM/Scl-75 cleavage for exosome function and the generation of anti-PM/Scl-75 autoantibodies are discussed. 相似文献
203.
Performance analysis of MPI collective operations 总被引:1,自引:0,他引:1
Jelena Pješivac-Grbović Thara Angskun George Bosilca Graham E. Fagg Edgar Gabriel Jack J. Dongarra 《Cluster computing》2007,10(2):127-143
Previous studies of application usage show that the performance of collective communications are critical for high-performance
computing. Despite active research in the field, both general and feasible solution to the optimization of collective communication
problem is still missing.
In this paper, we analyze and attempt to improve intra-cluster collective communication in the context of the widely deployed
MPI programming paradigm by extending accepted models of point-to-point communication, such as Hockney, LogP/LogGP, and PLogP,
to collective operations. We compare the predictions from models against the experimentally gathered data and using these
results, construct optimal decision function for broadcast collective. We quantitatively compare the quality of the model-based
decision functions to the experimentally-optimal one. Additionally, in this work, we also introduce a new form of an optimized
tree-based broadcast algorithm, splitted-binary.
Our results show that all of the models can provide useful insights into various aspects of the different algorithms as well
as their relative performance. Still, based on our findings, we believe that the complete reliance on models would not yield
optimal results. In addition, our experimental results have identified the gap parameter as being the most critical for accurate
modeling of both the classical point-to-point-based pipeline and our extensions to fan-out topologies.
相似文献
Jack J. DongarraEmail: |
204.
Ward Delphi Melbourne-Thomas Jessica Pecl Gretta T. Evans Karen Green Madeline McCormack Phillipa C. Novaglio Camilla Trebilco Rowan Bax Narissa Brasier Madeleine J. Cavan Emma L. Edgar Graham Hunt Heather L. Jansen Jan Jones Russ Lea Mary-Anne Makomere Reuben Mull Chris Semmens Jayson M. Shaw Janette Tinch Dugald van Steveninck Tatiana J. Layton Cayne 《Reviews in Fish Biology and Fisheries》2022,32(1):65-100
Reviews in Fish Biology and Fisheries - Marine ecosystems and their associated biodiversity sustain life on Earth and hold intrinsic value. Critical marine ecosystem services include maintenance of... 相似文献
205.
R Moriggi Jr HS Di Mauro SC Dias JM Matos MB Urtado NF Camar?o IV Sousa Neto DC Nascimento RA Tibana CO Assump??o J Prestes CB Urtado 《Biology of sport / Institute of Sport》2015,32(4):289-294
Low intensity resistance exercise (RE) with blood flow restriction (BFR) has gained attention in the literature due to the beneficial effects on functional and morphological variables, similar to those observed during traditional RE without BFR, while the effects of BFR on post-exercise hypotension remain unclear. The aim of the present study was to compare the blood pressure (BP) response of trained normotensive individuals to RE with and without BFR. In this cross-over randomized trial, eight male subjects (23.8 ± 4 years, 74 ± 3 kg, 174 ± 4 cm) completed two exercise protocols: traditional RE (3 x 10 repetitions at 70% one-repetition maximum [1-RM]) and low intensity RE (3 x 15 repetitions at 20% 1-RM) with BFR. Blood pressure measurements were performed after 15 min of seated rest (0), immediately after and 10 min, 20 min, 30 min, 40 min, 50 min and 60 min after the experimental sessions. Similar hypotensive effects for systolic BP (SBP) were observed for both protocols (P < 0.05) after exercise, with no differences between groups (P > 0.05) and no statistically significant difference for diastolic BP (P > 0.05). These results suggest that in normotensive trained individuals, both traditional RE and RE with BFR induce hypotension for SBP, which is important to prevent cardiovascular disturbances. 相似文献
206.
JI Priego AG Lucas-Cuevas I Aparicio JV Giménez JM Cortell-Tormo P Pérez-Soriano 《Biology of sport / Institute of Sport》2015,32(3):219-223
The use of graduated compression stockings (GCS) in sport has been increasing in the last years due to their potential positive effects for athletes. However, there is little evidence to support whether these types of garments actually improve cardiorespiratory performance. The aim of this study was to examine the cardiorespiratory responses of GCS during running after three weeks of regular use. Twenty recreational runners performed three tests on different days: test 1) – a 5-min maximal effort run in order to determine the participants’ maximal aerobic speed; and tests 2) and 3) – a fatigue running test of 30 minutes at 80% of their maximal aerobic speed with either GCS or PLACEBO stockings at random. Cardiorespiratory parameters (minute ventilation, heart rate, relative oxygen consumption, relative carbon dioxide production, ventilatory equivalents for oxygen and carbon dioxide, and oxygen pulse) were measured. Before each test in the laboratory, the participants trained with the randomly assigned stockings (GCS or PLACEBO) for three weeks. No significant differences between GCS and PLACEBO were found in any of the cardiorespiratory parameters. In conclusion, the present study provides evidence that running with GCS for three weeks does not influence cardiorespiratory parameters in recreational runners. 相似文献
207.
Glucosylceramides are critical for cell‐type differentiation and organogenesis,but not for cell viability in Arabidopsis
下载免费PDF全文
![点击此处可从《The Plant journal : for cell and molecular biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Joseph Msanne Ming Chen Kyle D. Luttgeharm Amanda M. Bradley Elizabeth S. Mays Janet M. Paper Daniel L. Boyle Rebecca E. Cahoon Kathrin Schrick Edgar B. Cahoon 《The Plant journal : for cell and molecular biology》2015,84(1):188-201
Glucosylceramides (GlcCer), glucose‐conjugated sphingolipids, are major components of the endomembrane system and plasma membrane in most eukaryotic cells. Yet the quantitative significance and cellular functions of GlcCer are not well characterized in plants and other multi‐organ eukaryotes. To address this, we examined Arabidopsis lines that were lacking or deficient in GlcCer by insertional disruption or by RNA interference (RNAi) suppression of the single gene for GlcCer synthase (GCS, At2g19880), the enzyme that catalyzes GlcCer synthesis. Null mutants for GCS (designated ‘gcs‐1’) were viable as seedlings, albeit strongly reduced in size, and failed to develop beyond the seedling stage. Heterozygous plants harboring the insertion allele exhibited reduced transmission through the male gametophyte. Undifferentiated calli generated from gcs‐1 seedlings and lacking GlcCer proliferated in a manner similar to calli from wild‐type plants. However, gcs‐1 calli, in contrast to wild‐type calli, were unable to develop organs on differentiation media. Consistent with a role for GlcCer in organ‐specific cell differentiation, calli from gcs‐1 mutants formed roots and leaves on media supplemented with the glucosylated sphingosine glucopsychosine, which was readily converted to GlcCer independent of GCS. Underlying these phenotypes, gcs‐1 cells had altered Golgi morphology and fewer cisternae per Golgi apparatus relative to wild‐type cells, indicative of protein trafficking defects. Despite seedling lethality in the null mutant, GCS RNAi suppression lines with ≤2% of wild‐type GlcCer levels were viable and fertile. Collectively, these results indicate that GlcCer are essential for cell‐type differentiation and organogenesis, and plant cells produce amounts of GlcCer in excess of that required for normal development. 相似文献
208.
Markus Schueler Daniela?A. Braun Gayathri Chandrasekar Heon?Yung Gee Timothy?D. Klasson Jan Halbritter Andrea Bieder Jonathan?D. Porath Rannar Airik Weibin Zhou Joseph?J. LoTurco Alicia Che Edgar?A. Otto Detlef B?ckenhauer Neil?J. Sebire Tomas Honzik Peter?C. Harris Sarah?J. Koon Meral Gunay-Aygun Sophie Saunier Klaus Zerres Nadina?Ortiz Bruechle Joost?P.H. Drenth Laurence Pelletier Isabel Tapia-Páez Richard?P. Lifton Rachel?H. Giles Juha Kere Friedhelm Hildebrandt 《American journal of human genetics》2015,96(1):81-92
Nephronophthisis-related ciliopathies (NPHP-RC) are recessive diseases characterized by renal dysplasia or degeneration. We here identify mutations of DCDC2 as causing a renal-hepatic ciliopathy. DCDC2 localizes to the ciliary axoneme and to mitotic spindle fibers in a cell-cycle-dependent manner. Knockdown of Dcdc2 in IMCD3 cells disrupts ciliogenesis, which is rescued by wild-type (WT) human DCDC2, but not by constructs that reflect human mutations. We show that DCDC2 interacts with DVL and DCDC2 overexpression inhibits β-catenin-dependent Wnt signaling in an effect additive to Wnt inhibitors. Mutations detected in human NPHP-RC lack these effects. A Wnt inhibitor likewise restores ciliogenesis in 3D IMCD3 cultures, emphasizing the importance of Wnt signaling for renal tubulogenesis. Knockdown of dcdc2 in zebrafish recapitulates NPHP-RC phenotypes, including renal cysts and hydrocephalus, which is rescued by a Wnt inhibitor and by WT, but not by mutant, DCDC2. We thus demonstrate a central role of Wnt signaling in the pathogenesis of NPHP-RC, suggesting an avenue for potential treatment of NPHP-RC. 相似文献
209.
210.
Narayan S Carlson EM Cheng H Condon K Du H Eckley S Hu Y Jiang Y Kumar V Lewis BM Saxton P Schuck E Seletsky BM Tendyke K Zhang H Zheng W Littlefield BA Towle MJ Yu MJ 《Bioorganic & medicinal chemistry letters》2011,21(6):1634-1638
Eribulin mesylate is a newly approved treatment for locally advanced and metastatic breast cancer. We targeted oral bioavailability and efficacy against multidrug resistant (MDR) tumors for further work. The design, synthesis and evaluation of novel amine-containing analogs of eribulin mesylate are described in this part. Attenuation of basicity of the amino group(s) in the C32 side-chain region led to compounds with low susceptibility to PgP-mediated drug efflux. These compounds were active against MDR tumor cell lines in vitro and in xenograft models in vivo, in addition to being orally bioavailable. 相似文献