全文获取类型
收费全文 | 17891篇 |
免费 | 1782篇 |
国内免费 | 5篇 |
专业分类
19678篇 |
出版年
2022年 | 217篇 |
2021年 | 392篇 |
2020年 | 216篇 |
2019年 | 267篇 |
2018年 | 338篇 |
2017年 | 285篇 |
2016年 | 490篇 |
2015年 | 858篇 |
2014年 | 866篇 |
2013年 | 1013篇 |
2012年 | 1319篇 |
2011年 | 1308篇 |
2010年 | 785篇 |
2009年 | 700篇 |
2008年 | 968篇 |
2007年 | 958篇 |
2006年 | 935篇 |
2005年 | 845篇 |
2004年 | 819篇 |
2003年 | 767篇 |
2002年 | 689篇 |
2001年 | 191篇 |
2000年 | 174篇 |
1999年 | 213篇 |
1998年 | 250篇 |
1997年 | 162篇 |
1996年 | 163篇 |
1995年 | 148篇 |
1994年 | 131篇 |
1993年 | 161篇 |
1992年 | 172篇 |
1991年 | 138篇 |
1990年 | 150篇 |
1989年 | 119篇 |
1988年 | 131篇 |
1987年 | 133篇 |
1986年 | 110篇 |
1985年 | 112篇 |
1984年 | 125篇 |
1983年 | 119篇 |
1982年 | 115篇 |
1981年 | 99篇 |
1980年 | 95篇 |
1979年 | 86篇 |
1978年 | 69篇 |
1977年 | 65篇 |
1976年 | 84篇 |
1975年 | 77篇 |
1974年 | 97篇 |
1973年 | 74篇 |
排序方式: 共有10000条查询结果,搜索用时 0 毫秒
991.
Weiss E 《American journal of physical anthropology》2007,133(3):931-940
Anthropologists frequently use musculoskeletal stress markers to reconstruct past activity patterns. Yet, researchers have called into question the reliability of muscle marker measurements in part because body size and age affect muscle marker scores. In this study, the author examined an aggregate upper limb muscle marker to determine if after controlling for the effects of body size and age, one could reconstruct activity patterns of a prehistoric Amerind population. Analyses were made of a sample of 102 (43 males, 59 females) prehistoric central California Amerinds. Muscle markers were measured using two-point observer rating scales; body size was measured by humeral articular surfaces; age and sex were determined previously through standard procedures. Using sex separated rankings and partial correlations, disaggregated muscle markers were examined for correlations with age and size to determine if specific muscle markers may be useful in pinpointing to activity patterns. Aggregate upper limb muscle marker correlated with: age, r = 0.44; humeral size, r = 0.44; and sex, r = 0.43; Ps < 0.001. Older individuals had greater muscle markers, as did larger individuals, and males. Rankings seemed to be confounded by the effect size had on the muscle markers. However, based on partial correlations controlling for size and age, the differences that remained between males and females could be used to reconstruct male activities of throwing in hunting and interpersonal aggression acts. 相似文献
992.
We have identified 24 members of the DnaK subfamily of heat shock 70 proteins (Hsp70s) in the complete genomes of 5 diverse photosynthetic eukaryotes. The Hsp70s are a ubiquitous protein family that is highly conserved across all domains of life. Eukaryotic Hsp70s are found in a number of subcellular compartments in the cell: cytoplasm, mitochondrion (MT), chloroplast (CP), and endoplasmic reticulum (ER). Although the Hsp70s have been the subject of intense study in model organisms, very little is known of the Hsp70s from early diverging photosynthetic lineages. The sequencing of the complete genomes of Thalassiosira pseudonana (a diatom), Cyanidioschyzon merolae (a red alga), and 3 green algae (Chlamydomonas reinhardtii, Ostreococcus lucimarinus, Ostreococcus tauri) allow us to conduct comparative genomics of the Hsp70s present in these diverse photosynthetic eukaryotes. We have found that the distinct lineages of Hsp70s (MT, CP, ER, and cytoplasmic) each have different evolutionary histories. In general, evolutionary patterns of the mitochondrial and endoplasmic reticulum Hsp70s are relatively stable even among very distantly related organisms. This is not true of the chloroplast Hsp70s and we discuss the distinct evolutionary patterns between "green" and "red" plastids. Finally, we find that, in contrast to the angiosperms Arabidopsis thaliana and Oryza sativa that have numerous cytoplasmic Hsp70, the 5 algal species have only 1 cytoplasmic Hsp70 each. The evolutionary and functional implications of these differences are discussed. 相似文献
993.
Oosterveen T Coudreuse DY Yang PT Fraser E Bergsma J Dale TC Korswagen HC 《Developmental biology》2007,308(2):438-448
Axin is a central component of the canonical Wnt signaling pathway that interacts with the adenomatous polyposis coli protein APC and the kinase GSK3beta to downregulate the effector beta-catenin. In the nematode Caenorhabditis elegans, canonical Wnt signaling is negatively regulated by the highly divergent Axin ortholog PRY-1. Mutation of pry-1 leads to constitutive activation of BAR-1/beta-catenin-dependent Wnt signaling and results in a range of developmental defects. The pry-1 null phenotype is however not fully penetrant, indicating that additional factors may partially compensate for PRY-1 function. Here, we report the cloning and functional analysis of a second Axin-like protein, which we named AXL-1. We show that despite considerable sequence divergence with PRY-1 and other Axin family members, AXL-1 is a functional Axin ortholog. AXL-1 functions redundantly with PRY-1 in negatively regulating BAR-1/beta-catenin signaling in the developing vulva and the Q neuroblast lineage. In addition, AXL-1 functions independently of PRY-1 in negatively regulating canonical Wnt signaling during excretory cell development. In contrast to vertebrate Axin and the related protein Conductin, AXL-1 and PRY-1 are not functionally equivalent. We conclude that Axin function in C. elegans is divided over two different Axin orthologs that have specific functions in negatively regulating canonical Wnt signaling. 相似文献
994.
Walker EA Ahmed A Lavery GG Tomlinson JW Kim SY Cooper MS Ride JP Hughes BA Shackleton CH McKiernan P Elias E Chou JY Stewart PM 《The Journal of biological chemistry》2007,282(37):27030-27036
Microsomal glucose-6-phosphatase-alpha (G6Pase-alpha) and glucose 6-phosphate transporter (G6PT) work together to increase blood glucose concentrations by performing the terminal step in both glycogenolysis and gluconeogenesis. Deficiency of the G6PT in liver gives rise to glycogen storage disease type 1b (GSD1b), whereas deficiency of G6Pase-alpha leads to GSD1a. G6Pase-alpha shares its substrate (glucose 6-phosphate; G6P) with hexose-6-phosphate-dehydrogenase (H6PDH), a microsomal enzyme that regenerates NADPH within the endoplasmic reticulum lumen, thereby conferring reductase activity upon 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). 11beta-HSD1 interconverts hormonally active C11beta-hydroxy steroids (cortisol in humans and corticosterone in rodents) to inactive C11-oxo steroids (cortisone and 11-dehydrocorticosterone, respectively). In vivo reductase activity predominates, generating active glucocorticoid. We hypothesized that substrate (G6P) availability to H6PDH in patients with GSD1b and GSD1a will decrease or increase 11beta-HSD1 reductase activity, respectively. We investigated 11beta-HSD1 activity in GSD1b and GSD1a mice and in two patients with GSD1b and five patients diagnosed with GSD1a. We confirmed our hypothesis by assessing 11beta-HSD1 in vivo and in vitro, revealing a significant decrease in reductase activity in GSD1b animals and patients, whereas GSD1a patients showed a marked increase in activity. The cellular trafficking of G6P therefore directly regulates 11beta-HSD1 reductase activity and provides a novel link between glucose metabolism and function of the hypothalamo-pituitary-adrenal axis. 相似文献
995.
996.
Zhu Q Krakowski AR Dunham EE Wang L Bandyopadhyay A Berdeaux R Martin GS Sun L Luo K 《Molecular and cellular biology》2007,27(1):324-339
SnoN is an important negative regulator of transforming growth factor beta signaling through its ability to interact with and repress the activity of Smad proteins. It was originally identified as an oncoprotein based on its ability to induce anchorage-independent growth in chicken embryo fibroblasts. However, the roles of SnoN in mammalian epithelial carcinogenesis have not been well defined. Here we show for the first time that SnoN plays an important but complex role in human cancer. SnoN expression is highly elevated in many human cancer cell lines, and this high level of SnoN promotes mitogenic transformation of breast and lung cancer cell lines in vitro and tumor growth in vivo, consistent with its proposed pro-oncogenic role. However, this high level of SnoN expression also inhibits epithelial-to-mesenchymal transdifferentiation. Breast and lung cancer cells expressing the shRNA for SnoN exhibited an increase in cell motility, actin stress fiber formation, metalloprotease activity, and extracellular matrix production as well as a reduction in adherens junction proteins. Supporting this observation, in an in vivo breast cancer metastasis model, reducing SnoN expression was found to moderately enhance metastasis of human breast cancer cells to bone and lung. Thus, SnoN plays both pro-tumorigenic and antitumorigenic roles at different stages of mammalian malignant progression. The growth-promoting activity of SnoN appears to require its ability to bind to and repress the Smad proteins, while the antitumorigenic activity can be mediated by both Smad-dependent and Smad-independent pathways and requires the activity of small GTPase RhoA. Our study has established the importance of SnoN in mammalian epithelial carcinogenesis and revealed a novel aspect of SnoN function in malignant progression. 相似文献
997.
998.
999.
1000.