全文获取类型
收费全文 | 1014篇 |
免费 | 107篇 |
专业分类
1121篇 |
出版年
2023年 | 6篇 |
2022年 | 12篇 |
2021年 | 24篇 |
2020年 | 16篇 |
2019年 | 23篇 |
2018年 | 25篇 |
2017年 | 19篇 |
2016年 | 44篇 |
2015年 | 55篇 |
2014年 | 67篇 |
2013年 | 88篇 |
2012年 | 91篇 |
2011年 | 82篇 |
2010年 | 58篇 |
2009年 | 37篇 |
2008年 | 68篇 |
2007年 | 51篇 |
2006年 | 38篇 |
2005年 | 47篇 |
2004年 | 48篇 |
2003年 | 49篇 |
2002年 | 48篇 |
2001年 | 9篇 |
2000年 | 10篇 |
1999年 | 10篇 |
1998年 | 11篇 |
1997年 | 10篇 |
1996年 | 5篇 |
1995年 | 5篇 |
1994年 | 2篇 |
1993年 | 7篇 |
1992年 | 5篇 |
1991年 | 2篇 |
1990年 | 4篇 |
1987年 | 2篇 |
1983年 | 3篇 |
1982年 | 5篇 |
1979年 | 5篇 |
1977年 | 5篇 |
1976年 | 2篇 |
1971年 | 1篇 |
1947年 | 1篇 |
1936年 | 1篇 |
1932年 | 3篇 |
1931年 | 2篇 |
1929年 | 3篇 |
1926年 | 1篇 |
1925年 | 1篇 |
1924年 | 1篇 |
1920年 | 2篇 |
排序方式: 共有1121条查询结果,搜索用时 0 毫秒
31.
Todd J. Brinkman Michael K. Schwartz David K. Person Kristine L. Pilgrim Kris J. Hundertmark 《Conservation Genetics》2010,11(4):1547-1552
Non-invasive wildlife research using DNA from feces has become increasingly popular. Recent studies have attempted to solve
problems associated with recovering DNA from feces by investigating the influence of factors such as season, diet, collection
method, preservation method, extraction protocol, and time. To our knowledge, studies of this nature have not addressed DNA
degradation over time in wet environments, and have not been performed on fecal pellets of ungulates. Therefore, our objective
was to determine the length of time a fecal pellet from a Sitka black-tailed deer (Odocoileus hemionus sitkensis) could remain in the field in a temperate rainforest environment before the DNA became too degraded for individual identification.
Pellets were extracted from the rectum of recently killed deer and placed in an environment protected from rainfall and in
an environment exposed to rainfall. Pellets from each treatment group were sampled at intervals of 2, 7, 14, 21, and 28 days
after deer harvest. DNA was extracted from sampled pellets and individual samples were genotyped using microsatellite markers.
Amplification failure and errors (dropout and false alleles) were recorded to determine extent of DNA degradation. Eighty
percent of samples in the protected environment and 22% of samples in the exposed environment were successfully genotyped
during the 28-day experiment. With no samples being successfully genotyped in the exposed environment after 7 days, our study
showed that rainfall significantly increases degradation rates of DNA from ungulate pellets. 相似文献
32.
Pawel Nowak Derek C. Cole Ann Aulabaugh Jonathan Bard Rajiv Chopra Rebecca Cowling Kristi Y. Fan Baihua Hu Steve Jacobsen Minakshi Jani Guixan Jin Mei-Chu Lo Michael S. Malamas Eric S. Manas Rani Narasimhan Peter Reinhart Albert J. Robichaud Joseph R. Stock Joan Subrath Kristine Svenson John W. Ellingboe 《Bioorganic & medicinal chemistry letters》2010,20(2):632-635
8,8-Diphenyl-2,3,4,8-tetrahydroimidazo[1,5-a]pyrimidin-6-amine (1) was identified through HTS, as a weak (micromolar) inhibitor of BACE1. X-Ray crystallographic studies indicate the 2-aminoimidazole ring forms key H-bonding interactions with Asp32 and Asp228 in the catalytic site of BACE1. Lead optimization using structure-based focused libraries led to the identification of low nanomolar BACE1 inhibitors such as 20b with substituents which extend from the S1 to the S3 pocket. 相似文献
33.
Jody M. Tucker Michael K. Schwartz Richard L. Truex Kristine L. Pilgrim Fred W. Allendorf 《PloS one》2012,7(12)
Establishing if species contractions were the result of natural phenomena or human induced landscape changes is essential for managing natural populations. Fishers (Martes pennanti) in California occur in two geographically and genetically isolated populations in the northwestern mountains and southern Sierra Nevada. Their isolation is hypothesized to have resulted from a decline in abundance and distribution associated with European settlement in the 1800s. However, there is little evidence to establish that fisher occupied the area between the two extant populations at that time. We analyzed 10 microsatellite loci from 275 contemporary and 21 historical fisher samples (1880–1920) to evaluate the demographic history of fisher in California. We did not find any evidence of a recent (post-European) bottleneck in the northwestern population. In the southern Sierra Nevada, genetic subdivision within the population strongly influenced bottleneck tests. After accounting for genetic subdivision, we found a bottleneck signal only in the northern and central portions of the southern Sierra Nevada, indicating that the southernmost tip of these mountains may have acted as a refugium for fisher during the anthropogenic changes of the late 19th and early 20th centuries. Using a coalescent-based Bayesian analysis, we detected a 90% decline in effective population size and dated the time of decline to over a thousand years ago. We hypothesize that fisher distribution in California contracted to the two current population areas pre-European settlement, and that portions of the southern Sierra Nevada subsequently experienced another more recent bottleneck post-European settlement. 相似文献
34.
Pei Dong Jessica Flores Kristine Pelton Keith R. Solomon 《Journal of cellular biochemistry》2010,111(5):1367-1374
Cholesterol is essential in establishing most functional animal cell membranes; cells cannot grow or proliferate in the absence of sufficient cholesterol. Consequently, almost every cell, tissue, and animal tightly regulates cholesterol homeostasis, including complex mechanisms of synthesis, transport, uptake, and disposition of cholesterol molecules. We hypothesize that cellular recognition of cholesterol insufficiency causes cell cycle arrest in order to avoid a catastrophic failure in membrane synthesis. Here, we demonstrate using unbiased proteomics and standard biochemistry that cholesterol insufficiency causes upregulation of prohibitin, an inhibitor of cell cycle progression, through activation of a cholesterol‐responsive promoter element. We also demonstrate that prohibitin protects cells from apoptosis caused by cholesterol insufficiency. This is the first study tying cholesterol homeostasis to a specific cell cycle regulator that inhibits apoptosis. J. Cell. Biochem. 111: 1367–1374, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
35.
Enhanced skeletal muscle contraction with myosin light chain phosphorylation by a calmodulin-sensing kinase 总被引:2,自引:0,他引:2
Repetitive low frequency stimulation results in potentiation of twitch force development in fast-twitch skeletal muscle due to myosin regulatory light chain (RLC) phosphorylation by Ca(2+)/calmodulin (CaM)-dependent skeletal muscle myosin light chain kinase (skMLCK). We generated transgenic mice that express an skMLCK CaM biosensor in skeletal muscle to determine whether skMLCK or CaM is limiting to twitch force potentiation. Three transgenic mouse lines exhibited up to 22-fold increases in skMLCK protein expression in fast-twitch extensor digitorum longus muscle containing type IIa and IIb fibers, with comparable expressions in slow-twitch soleus muscle containing type I and IIa fibers. The high expressing lines showed a more rapid RLC phosphorylation and force potentiation in extensor digitorum longus muscle with low frequency electrical stimulation. Surprisingly, overexpression of skMLCK in soleus muscle did not recapitulate the fast-twitch potentiation response despite marked enhancement of both fast-twitch and slow-twitch RLC phosphorylation. Analysis of calmodulin binding to the biosensor showed a frequency-dependent activation to a maximal extent of 60%. Because skMLCK transgene expression is 22-fold greater than the wild-type kinase, skMLCK rather than calmodulin is normally limiting for RLC phosphorylation and twitch force potentiation. The kinase activation rate (10.6 s(-1)) was only 3.6-fold slower than the contraction rate, whereas the inactivation rate (2.8 s(-1)) was 12-fold slower than relaxation. The slower rate of kinase inactivation in vivo with repetitive contractions provides a biochemical memory via RLC phosphorylation. Importantly, RLC phosphorylation plays a prominent role in skeletal muscle force potentiation of fast-twitch type IIb but not type I or IIa fibers. 相似文献
36.
Thomas R. Jackson Kristine Salmina Anda Huna Inna Inashkina Eriks Jankevics Una Riekstina Zane Kalnina Andrey Ivanov Paul A. Townsend Mark S. Cragg Jekaterina Erenpreisa 《Cell cycle (Georgetown, Tex.)》2013,12(3):430-431
Comment on: Wu R, et al. Clin Cancer Res 2011; 17:7359–72 相似文献
37.
Kristine Y. Crous Audrey G. Quentin Yan‐Shih Lin Belinda E. Medlyn David G. Williams Craig V. M. Barton David S. Ellsworth 《Global Change Biology》2013,19(12):3790-3807
Eucalyptus species are grown widely outside of their native ranges in plantations on all vegetated continents of the world. We predicted that such a plantation species would show high potential for acclimation of photosynthetic traits across a wide range of growth conditions, including elevated [CO2] and climate warming. To test this prediction, we planted temperate Eucalyptus globulus Labill. seedlings in climate‐controlled chambers in the field located >700 km closer to the equator than the nearest natural occurrence of this species. Trees were grown in a complete factorial combination of elevated CO2 concentration (eC; ambient [CO2] +240 ppm) and air warming treatments (eT; ambient +3 °C) for 15 months until they reached ca. 10 m height. There was little acclimation of photosynthetic capacity to eC and hence the CO2‐induced photosynthetic enhancement was large (ca. 50%) in this treatment during summer. The warming treatment significantly increased rates of both carboxylation capacity (Vcmax) and electron transport (Jmax) (measured at a common temperature of 25 °C) during winter, but decreased them significantly by 20–30% in summer. The photosynthetic CO2 compensation point in the absence of dark respiration (Γ*) was relatively less sensitive to temperature in this temperate eucalypt species than for warm‐season tobacco. The temperature optima for photosynthesis and Jmax significantly changed by about 6 °C between winter and summer, but without further adjustment from early to late summer. These results suggest that there is an upper limit for the photosynthetic capacity of E. globulus ssp. globulus outside its native range to acclimate to growth temperatures above 25 °C. Limitations to temperature acclimation of photosynthesis in summer may be one factor that defines climate zones where E. globulus plantation productivity can be sustained under anticipated global environmental change. 相似文献
38.
The immunohistochemical occurrence of sarafotoxin (SRTX), a snake venom peptide under strong evolutionary control, was investigated in the pulmonary diffuse neuroendocrine system (PDNES) of newborn cats and rats. By applying the avidin-biotin-peroxidase complex method on serial lung sections, we have demonstrated its distribution and colocalization with different endothelin (ET) isoforms. A light microscopic study revealed apparent immunostaining for SRTX in neuronal components and smooth muscle tissue and in neuroepithelial bodies (NEB), while isolated neuroendocrine cells (NEC) remain unlabelled. Comparison of the SRTX reactivity pattern with that of different ET peptides on adjacent lung sections showed colocalization of SRTX-b with ET-3 in NEB, intrapulmonary ganglion cells and nerve fibres, on the one hand, and with ET-1 in airway and vascular smooth muscle cells, on the other. These findings, in addition to the remarkable functional and structural similarities between SRTX and ET peptides, suggest a common evolutionary origin and biological significance of sarafotoxin and endothelins. Moreover, this is the first time that a toxic peptide has been demonstrated in the PDNES. 相似文献
39.
Harden CJ Perez-Carrion K Babakordi Z Plummer SF Hepburn N Barker ME Wright PC Evans CA Corfe BM 《Journal of Proteomics》2012,75(10):2916-2923
Current measurement of appetite depends upon tools that are either subjective (visual analogue scales), or invasive (blood). Saliva is increasingly recognised as a valuable resource for biomarker analysis. Proteomics workflows may provide alternative means for the assessment of appetitive response. The study aimed to assess the potential value of the salivary proteome to detect novel biomarkers of appetite using an iTRAQ-based workflow. Diurnal variation of salivary protein concentrations was assessed. A randomised, controlled, crossover study examined the effects on the salivary proteome of isocaloric doses of various long chain fatty acid (LCFA) oil emulsions compared to no treatment (NT). Fasted males provided saliva samples before and following NT or dosing with LCFA emulsions. The oil component of the DHA emulsion contained predominantly docosahexaenoic acid and the oil component of OA contained predominantly oleic acid. Several proteins were present in significantly (p<0.05) different quantities in saliva samples taken following treatments compared to fasting samples. DHA caused alterations in thioredoxin and serpin B4 relative to OA and NT. A further study evaluated energy intake (EI) in response to LCFA in conjunction with subjective appetite scoring. DHA was associated with significantly lower EI relative to NT and OA (p=0.039). The collective data suggest investigation of salivary proteome may be of value in appetitive response. This article is part of a Special Issue entitled: Proteomics: The clinical link. 相似文献