全文获取类型
收费全文 | 1511篇 |
免费 | 126篇 |
出版年
2024年 | 3篇 |
2023年 | 8篇 |
2022年 | 12篇 |
2021年 | 27篇 |
2020年 | 17篇 |
2019年 | 23篇 |
2018年 | 26篇 |
2017年 | 28篇 |
2016年 | 42篇 |
2015年 | 78篇 |
2014年 | 70篇 |
2013年 | 107篇 |
2012年 | 137篇 |
2011年 | 109篇 |
2010年 | 88篇 |
2009年 | 76篇 |
2008年 | 102篇 |
2007年 | 115篇 |
2006年 | 92篇 |
2005年 | 75篇 |
2004年 | 89篇 |
2003年 | 73篇 |
2002年 | 49篇 |
2001年 | 13篇 |
2000年 | 9篇 |
1999年 | 17篇 |
1998年 | 20篇 |
1997年 | 9篇 |
1996年 | 7篇 |
1995年 | 6篇 |
1994年 | 4篇 |
1993年 | 6篇 |
1992年 | 2篇 |
1991年 | 6篇 |
1990年 | 4篇 |
1989年 | 3篇 |
1988年 | 7篇 |
1987年 | 6篇 |
1986年 | 7篇 |
1985年 | 5篇 |
1984年 | 12篇 |
1983年 | 6篇 |
1982年 | 7篇 |
1981年 | 4篇 |
1980年 | 2篇 |
1979年 | 4篇 |
1974年 | 4篇 |
1973年 | 9篇 |
1968年 | 4篇 |
1910年 | 2篇 |
排序方式: 共有1637条查询结果,搜索用时 250 毫秒
101.
Cailu Lin Brad D. Fesi Michael Marquis Natalia P. Bosak Maria L. Theodorides Mauricio Avigdor Amanda H. McDaniel Fujiko F. Duke Anna Lysenko Amin Khoshnevisan Brian R. Gantick Charles J. Arayata Theodore M. Nelson Alexander A. Bachmanov Danielle R. Reed 《PloS one》2015,10(11)
Genetic variation contributes to individual differences in obesity, but defining the exact relationships between naturally occurring genotypes and their effects on fatness remains elusive. As a step toward positional cloning of previously identified body composition quantitative trait loci (QTLs) from F2 crosses of mice from the C57BL/6ByJ and 129P3/J inbred strains, we sought to recapture them on a homogenous genetic background of consomic (chromosome substitution) strains. Male and female mice from reciprocal consomic strains originating from the C57BL/6ByJ and 129P3/J strains were bred and measured for body weight, length, and adiposity. Chromosomes 2, 7, and 9 were selected for substitution because previous F2 intercross studies revealed body composition QTLs on these chromosomes. We considered a QTL confirmed if one or both sexes of one or both reciprocal consomic strains differed significantly from the host strain in the expected direction after correction for multiple testing. Using these criteria, we confirmed two of two QTLs for body weight (Bwq5-6), three of three QTLs for body length (Bdln3-5), and three of three QTLs for adiposity (Adip20, Adip26 and Adip27). Overall, this study shows that despite the biological complexity of body size and composition, most QTLs for these traits are preserved when transferred to consomic strains; in addition, studying reciprocal consomic strains of both sexes is useful in assessing the robustness of a particular QTL. 相似文献
102.
Pedro Del Bianco Benedeti Lorrayny Galoro da Silva Eduardo Marostegan de Paula Teshome Shenkoru Marcos Inácio Marcondes Hugo Fernando Monteiro Brad Amorati Yenling Yeh Simon Roger Poulson Antonio Pinheiro Faciola 《PloS one》2015,10(11)
The objective of this study was to evaluate the effects of partially replacing dry ground corn with glycerin on ruminal fermentation using a dual-flow continuous culture system. Six fermenters (1,223 ± 21 ml) were used in a replicated 3x3 Latin square arrangement with three periods of 10 d each, with 7 d for diet adaptation and 3 d for sample collections. All diets contained 75% concentrate and three dietary glycerin levels (0, 15, and 30% on dry matter basis), totaling six replicates per treatment. Fermenters were fed 72 g of dry matter/d equally divided in two meals/d, at 0800 and 2000 h. Solid and liquid dilution rates were adjusted daily to 5.5 and 11%/h, respectively. On d 8, 9, and 10, samples of 500 ml of solid and liquid digesta effluent were mixed, homogenized, and stored at -20°C. Subsamples of 10 ml were collected and preserved with 0.2 mL of a 50% H2SO4 solution for later determination of NH3-N and volatile fatty acids. Microbial biomass was isolated from fermenters for chemical analysis at the end of each experimental period. Data were analyzed using the MIXED procedure in SAS with α = 0.05. Glycerin levels did not affect apparent digestibility of DM (P
Lin. = 0.13; P
Quad. = 0.40), OM (P
Lin. = 0.72; P
Quad. = 0.15), NDF (P
Lin. = 0.38; P
Quad. = 0.50) and ADF (P
Lin. = 0.91; P
Quad. = 0.18). Also, glycerin inclusion did not affect true digestibility of DM (P
Lin. = 0.35; P
Quad. = 0.48), and OM (P
Lin. = 0.08; P
Quad. = 0.19). Concentrations of propionate (P < 0.01) and total volatile fatty acids (P < 0.01) increased linearly and concentrations of acetate (P < 0.01), butyrate (P = 0.01), iso-valerate (P < 0.01), and total branched-chain volatile fatty acids, as well as the acetate: propionate ratio (P < 0.01) decreased with glycerin inclusion. Linear increases on NH3-N concentration in digesta effluent (P < 0.01) and on NH3-N flow (P < 0.01) were observed due to glycerin inclusion in the diets. Crude protein digestibility (P = 0.04) and microbial N flow (P = 0.04) were greater in the control treatment compared with the other treatments and responded quadratically with glycerin inclusion. Furthermore, the inclusion of glycerin linearly decreased (P = 0.02) non-ammonia N flow. Glycerin levels did not affect the flows of total N (P
Lin. = 0.79; P
Quad. = 0.35), and dietary N (P
Lin. = 0.99; P
Quad. = 0.07), as well as microbial efficiency (P
Lin. = 0.09; P
Quad. = 0.07). These results suggest that partially replacing dry ground corn with glycerin may change ruminal fermentation, by increasing total volatile fatty acids, and propionate concentration without affecting microbial efficiency, which may improve glucogenic potential of beef cattle diets. 相似文献
103.
Yanqin Ren Szu Han Huang Amanda B. Macedo Adam R. Ward Winiffer D. Conce Alberto Thais Klevorn Louise Leyre Dennis C. Copertino Talia M. Mota Dora Chan Ronald Truong Thomas Rohwetter Paul Zumbo Friederike Dündar Doron Betel Colin Kovacs Erika Benko Alberto Bosque R. Brad Jones 《Journal of virology》2021,95(15)
104.
Marina L Kozak Alejandro Chavez Weiwei Dang Shelley L Berger Annie Ashok Xiaoge Guo F Brad Johnson 《The EMBO journal》2010,29(1):158-170
Changes in telomere chromatin have been linked to cellular senescence, but the underlying mechanisms and impact on lifespan are unclear. We found that inactivation of the Sas2 histone acetyltransferase delays senescence in Saccharomyces cerevisiae telomerase (tlc1) mutants through a homologous recombination‐dependent mechanism. Sas2 acetylates histone H4 lysine 16 (H4K16), and telomere shortening in tlc1 mutants was accompanied by a selective and Sas2‐dependent increase in subtelomeric H4K16 acetylation. Further, mutation of H4 lysine 16 to arginine, which mimics constitutively deacetylated H4K16, delayed senescence and was epistatic to sas2 deletion, indicating that deacetylated H4K16 mediates the delay caused by sas2 deletion. Sas2 normally prevents the Sir2/3/4 heterochromatin complex from leaving the telomere and spreading to internal euchromatic loci. Senescence was delayed by sir3 deletion, but not sir2 deletion, indicating that senescence delay is mediated by release of Sir3 specifically from the telomere repeats. In contrast, sir4 deletion sped senescence and blocked the delay conferred by sas2 or sir3 deletion. We thus show that manipulation of telomere chromatin modulates senescence caused by telomere shortening. 相似文献
105.
106.
Feng V. Yang William D. Shipe Jaime L. Bunda M. Brad Nolt David D. Wisnoski Zhijian Zhao James C. Barrow William J. Ray Lei Ma Marion Wittmann Matthew A. Seager Kenneth A. Koeplinger George D. Hartman Craig W. Lindsley 《Bioorganic & medicinal chemistry letters》2010,20(2):531-536
An iterative analog library synthesis approach was employed in the exploration of a quinolone carboxylic acid series of selective M1 positive allosteric modulators, and strategies for improving potency and plasma free fraction were identified. 相似文献
107.
Alyssa L Kennedy Tony McBryan Greg H Enders F Brad Johnson Rugang Zhang Peter D Adams 《Cell division》2010,5(1):1-11
Background
Cellular senescence is a permanent growth arrest that occurs in response to cellular stressors, such as telomere shortening or activation of oncogenes. Although the process of senescence growth arrest is somewhat conserved between mouse and human cells, there are some critical differences in the molecular pathways of senescence between these two species. Recent studies in human fibroblasts have defined a cell signaling pathway that is initiated by repression of a specific Wnt ligand, Wnt2. This, in turn, activates a histone chaperone HIRA, and culminates in formation of specialized punctate domains of facultative heterochromatin, called Senescence-Associated Heterochromatin Foci (SAHF), that are enriched in the histone variant, macroH2A. SAHF are thought to repress expression of proliferation-promoting genes, thereby contributing to senescence-associated proliferation arrest. We asked whether this Wnt2-HIRA-SAHF pathway is conserved in mouse fibroblasts.Results
We show that mouse embryo fibroblasts (MEFs) and mouse skin fibroblasts, do not form robust punctate SAHF in response to an activated Ras oncogene or shortened telomeres. However, senescent MEFs do exhibit elevated levels of macroH2A staining throughout the nucleus as a whole. Consistent with their failure to fully activate the SAHF assembly pathway, the Wnt2-HIRA signaling axis is not overtly regulated between proliferating and senescent mouse cells.Conclusions
In addition to the previously defined differences between mouse and human cells in the mechanisms and phenotypes associated with senescence, we conclude that senescent mouse and human fibroblasts also differ at the level of chromatin and the signaling pathways used to regulate chromatin. These differences between human and mouse senescence may contribute to the increased propensity of mouse fibroblasts (and perhaps other mouse cell types) to become immortalized and transformed, compared to human cells. 相似文献108.
Establishing the diets of marine generalist consumers is difficult, with most studies limited to the use of morphological methods for prey identification. Such analyses rely on the preservation of diagnostic hard parts, which can limit taxonomic resolution and introduce biases. DNA-based analyses provide a method to assess the diets of marine species, potentially overcoming many of the limitations introduced by other techniques. This study compared the effectiveness of morphological and DNA-based analysis for determining the diet of a free-ranging generalist predator, the arrow squid (Nototodarus gouldi). A combined approach was more effective than using either of the methods in isolation. Nineteen unique prey taxa were identified, of which six were found by both methods, 10 were only detected using DNA and three were only identified using morphological methods. Morphological techniques only found 50% of the total number of identifiable prey taxa, whereas DNA-based techniques found 84%. This study highlights the benefits of using a combination of techniques to detect and identify prey of generalist marine consumers. 相似文献
109.
110.
Parvadia JK Keswani SG Vaikunth S Maldonado AR Marwan A Stehr W Erwin C Uzvolgyi E Warner BW Yamano S Taichman N Crombleholme TM 《American journal of physiology. Gastrointestinal and liver physiology》2007,293(3):G591-G598
Previous work in our group has demonstrated that mouse salivary gland has the highest concentration of salivary-derived VEGF protein compared with other organs and is essential for normal palatal mucosal wound healing. We hypothesize that salivary VEGF plays an important role in maintaining the integrity of the gastrointestinal mucosa following small bowel resection (SBR). Thirty-five 8- to 10-wk-old C57BL/6 female mice were divided into seven treatment groups: 1) sham (transaction and anastomosis, n = 5); 2) SBR (n = 8); 3) sialoadenectomy and small bowel resection (SAL+SBR, n = 8); 4) sialoadenectomy and small bowel resection with EGF supplementation (SAL+SBR+EGF, n = 9); 5) sialoadenectomy and small bowel resection with VEGF supplementation (SAL+SBR+VEGF, n = 9); 6) sialoadenectomy and small bowel resection supplemented with EGF and VEGF (SAL+ SBR+VEGF+EGF, n = 6); 7) selective inhibition of VEGF in the submandibular gland by Ad-VEGF-Trap following small bowel resection (Ad-VEGF-Trap+SBR, n = 7). Adaptation was after 3 days by ileal villus height and crypt depth. The microvascular response was evaluated by CD31 immunostaining and for villus-vessel area ratio by FITC-labeled von Willebrand factor immunostaining. The adaptive response after SBR was significantly attenuated in the SAL group in terms of villus height (250.4 +/- 8.816 vs. 310 +/- 19.35, P = 0.01) and crypt depth (100.021 +/- 4.025 vs. 120.541 +/- 2.82, P = 0.01). This response was partially corrected by orogastric VEGF or EGF alone. The adaptive response was completely restored when both were administered together, suggesting that salivary VEGF and EGF both contribute to intestinal adaptation. VEGF increases the vascular density (6.4 +/- 0.29 vs. 6.1 +/- 0.29 vs. 5.96 +/- 0.20) and villus-vessel area ratio (0.713 +/- 0.01 vs. 0.73 +/- 0.01) in the adapting bowel. Supplementation of both EGF and VEGF fully rescues adaptation, suggesting that the adaptive response may be dependent on VEGF-driven angiogenesis. These results support a previously unrecognized role for VEGF in the small bowel adaptive response. 相似文献