全文获取类型
收费全文 | 3267篇 |
免费 | 393篇 |
专业分类
3660篇 |
出版年
2021年 | 43篇 |
2020年 | 29篇 |
2019年 | 31篇 |
2018年 | 38篇 |
2017年 | 49篇 |
2016年 | 46篇 |
2015年 | 116篇 |
2014年 | 114篇 |
2013年 | 120篇 |
2012年 | 141篇 |
2011年 | 141篇 |
2010年 | 93篇 |
2009年 | 95篇 |
2008年 | 106篇 |
2007年 | 116篇 |
2006年 | 115篇 |
2005年 | 126篇 |
2004年 | 101篇 |
2003年 | 129篇 |
2002年 | 97篇 |
2001年 | 82篇 |
2000年 | 76篇 |
1999年 | 70篇 |
1998年 | 40篇 |
1997年 | 40篇 |
1996年 | 33篇 |
1995年 | 39篇 |
1994年 | 42篇 |
1993年 | 33篇 |
1992年 | 64篇 |
1991年 | 74篇 |
1990年 | 63篇 |
1989年 | 83篇 |
1988年 | 61篇 |
1987年 | 67篇 |
1986年 | 50篇 |
1985年 | 44篇 |
1984年 | 61篇 |
1983年 | 40篇 |
1982年 | 36篇 |
1980年 | 38篇 |
1979年 | 50篇 |
1978年 | 48篇 |
1976年 | 39篇 |
1975年 | 32篇 |
1974年 | 42篇 |
1973年 | 41篇 |
1972年 | 33篇 |
1971年 | 30篇 |
1969年 | 28篇 |
排序方式: 共有3660条查询结果,搜索用时 15 毫秒
951.
952.
Gregory D. Cuny Maxime Robin Natalia P. Ulyanova Debasis Patnaik Valerie Pique Gilles Casano Ji-Feng Liu Xiangjie Lin Jun Xian Marcie A. Glicksman Ross L. Stein Jonathan M.G. Higgins 《Bioorganic & medicinal chemistry letters》2010,20(12):3491-3494
Haspin is a serine/threonine kinase required for completion of normal mitosis that is highly expressed during cell proliferation, including in a number of neoplasms. Consequently, it has emerged as a potential therapeutic target in oncology. A high throughput screen of approximately 140,000 compounds identified an acridine analog as a potent haspin kinase inhibitor. Profiling against a panel of 270 kinases revealed that the compound also exhibited potent inhibitory activity for DYRK2, another serine/threonine kinase. An optimization study of the acridine series revealed that the structure–activity relationship (SAR) of the acridine series for haspin and DYRK2 inhibition had many similarities. However, several structural differences were noted that allowed generation of a potent haspin kinase inhibitor (33, IC50 <60 nM) with 180-fold selectivity over DYRK2. In addition, a moderately potent DYRK2 inhibitor (41, IC50 <400 nM) with a 5.4-fold selectivity over haspin was also identified. 相似文献
953.
Anna M Schlagowski Katharina Knringer Sandrine Morlot Ana Snchez Vicente Tamara Flohr Lena Krmer Felix Boos Nabeel Khalid Sheraz Ahmed Jana Schramm Lena M Murschall Per Haberkant Frank Stein Jan Riemer Benedikt Westermann Ralf J Braun Konstanze F Winklhofer Gilles Charvin Johannes M Herrmann 《The EMBO journal》2021,40(16)
The formation of protein aggregates is a hallmark of neurodegenerative diseases. Observations on patient samples and model systems demonstrated links between aggregate formation and declining mitochondrial functionality, but causalities remain unclear. We used Saccharomyces cerevisiae to analyze how mitochondrial processes regulate the behavior of aggregation‐prone polyQ protein derived from human huntingtin. Expression of Q97‐GFP rapidly led to insoluble cytosolic aggregates and cell death. Although aggregation impaired mitochondrial respiration only slightly, it considerably interfered with the import of mitochondrial precursor proteins. Mutants in the import component Mia40 were hypersensitive to Q97‐GFP, whereas Mia40 overexpression strongly suppressed the formation of toxic Q97‐GFP aggregates both in yeast and in human cells. Based on these observations, we propose that the post‐translational import of mitochondrial precursor proteins into mitochondria competes with aggregation‐prone cytosolic proteins for chaperones and proteasome capacity. Mia40 regulates this competition as it has a rate‐limiting role in mitochondrial protein import. Therefore, Mia40 is a dynamic regulator in mitochondrial biogenesis that can be exploited to stabilize cytosolic proteostasis. 相似文献
954.
Giang T. H. Vu Thomas Wicker Jan P. Buchmann Peter M. Chandler Takashi Matsumoto Andreas Graner Nils Stein 《Functional & integrative genomics》2010,10(4):509-521
The barley mutant allele sdw3 confers a gibberellin-insensitive, semi-dwarf phenotype with potential for breeding of new semi-dwarfed barley cultivars.
Towards map-based cloning, sdw3 was delimited by high-resolution genetic mapping to a 0.04 cM interval in a “cold spot” of recombination of the proximal
region of the short arm of barley chromosome 2H. Extensive synteny between the barley Sdw3 locus (Hvu_sdw3) and the orthologous regions (Osa_sdw3, Sbi_sdw3, Bsy_sdw3) of three other grass species (Oryza sativa, Sorghum bicolor, Brachypodium sylvaticum) allowed for efficient synteny-based marker saturation in the target interval. Comparative sequence analysis revealed colinearity
for 23 out of the 38, 35, and 29 genes identified in Brachypodium, rice, and Sorghum, respectively. Markers co-segregating with Hvu_sdw3 were generated from two of these genes. Initial attempts at chromosome walking in barley were performed with seven orthologous
gene probes which were delimiting physical distances of 223, 123, and 127 kb in Brachypodium, rice, and Sorghum, respectively. Six non-overlapping small bacterial artificial chromosome (BAC) clone contigs (cumulative length of 670 kb)
were obtained, which indicated a considerably larger physical size of Hvu_sdw3. Low-pass sequencing of selected BAC clones from these barley contigs exhibited a substantially lower gene frequency per
physical distance and the presence of additional non-colinear genes. Four candidate genes for sdw3 were identified within barley BAC sequences that either co-segregated with the gene sdw3 or were located adjacent to these co-segregating genes. Identification of genic sequences in the sdw3 context provides tools for marker-assisted selection. Eventual identification of the actual gene will contribute new information
for a basic understanding of the mechanisms underlying growth regulation in barley. 相似文献
955.
Background
One challenge facing biologists is to tease out useful information from massive data sets for further analysis. A pathway-based analysis may shed light by projecting candidate genes onto protein functional relationship networks. We are building such a pathway-based analysis system. 相似文献956.
957.
Kees van Oers David S. Richardson Stein A. S?ther Jan Komdeur 《Journal of Ornithology》2010,151(1):69-77
Avian malaria can affect survival and reproduction of their hosts. Two patterns commonly observed in birds are that females
have a higher prevalence of malaria than do males and that prevalence decreases with age. The mechanisms behind these patterns
remain unclear. However, most studies on blood parasite infections are based on cross-sectional analyses of prevalence, ignoring
malaria related mortality and individual changes in infection. Here, we analyse both within-individual changes in malaria
prevalence and long-term survival consequences of infection in the Seychelles Warbler (Acrocephalus sechellensis). Adults were less likely to be infected than juveniles but, contrary to broad patterns previously reported in birds, females
were less likely to be infected than males. We show by screening individual birds in two subsequent years that the decline
with age is a result both of individual suppression of infection and selective mortality. Birds that were infected early in
life had a lower survival rate compared to uninfected birds, but among those that survived to be screened twice the proportion
of infected birds had also decreased. Uninfected birds did not become infected later in life. Males were found to be more
infected than females in this species possibly because, unlike most birds, males are the dispersing sex and the cost of dispersal
may have to be traded against immunity. Infected males took longer to suppress their infection than did females. We conclude
that these infections are indeed costly, and that age-related patterns in blood parasite prevalence are influenced both by
suppression and selective mortality. 相似文献
958.
Peter R. Jungblut Franziska Schiele Ursula Zimny‐Arndt Renate Ackermann Monika Schmid Sabine Lange Robert Stein Klaus‐Peter Pleissner 《Proteomics》2010,10(2):182-193
With its predicted proteome of 1550 proteins (data set Etalon) Helicobacter pylori 26695 represents a perfect model system of medium complexity for investigating basic questions in proteomics. We analyzed urea‐solubilized proteins by 2‐DE/MS (data set 2‐DE) and by 1‐DE‐LC/MS (Supprot); proteins insoluble in 9 M urea but solubilized by SDS (Pellet); proteins precipitating in the Sephadex layer at the application side of IEF (Sephadex) by 1‐DE‐LC/MS; and proteins precipitating close to the application side within the IEF gel by LC/MS (Startline). The experimental proteomics data of H. pylori comprising 567 proteins (protein coverage: 36.6%) were stored in the Proteome Database System for Microbial Research ( http://www.mpiib‐berlin.mpg.de/2D‐PAGE/ ), which gives access to raw mass spectra (MALDI‐TOF/TOF) in T2D format, as well as to text files of peak lists. For data mining the protein mapping and comparison tool PROMPT ( http://webclu.bio.wzw.tum.de/prompt/ ) was used. The percentage of proteins with transmembrane regions, relative to all proteins detected, was 0, 0.2, 0, 0.5, 3.8 and 6.3% for 2‐DE, Supprot, Startline, Sephadex, Pellet, and Etalon, respectively. 2‐DE does not separate membrane proteins because they are insoluble in 9 M urea/70 mM DTT and 2% CHAPS. SDS solubilizes a considerable portion of the urea‐insoluble proteins and makes them accessible for separation by SDS‐PAGE and LC. The 2‐DE/MS analysis with urea‐solubilized proteins and the 1‐DE‐LC/MS analysis with the urea‐insoluble protein fraction (Pellet) are complementary procedures in the pursuit of a complete proteome analysis. Access to the PROMPT‐generated diagrams in the Proteome Database allows the mining of experimental data with respect to other functional aspects. 相似文献
959.
960.