全文获取类型
收费全文 | 1121篇 |
免费 | 238篇 |
出版年
2021年 | 13篇 |
2018年 | 13篇 |
2017年 | 12篇 |
2016年 | 18篇 |
2015年 | 38篇 |
2014年 | 37篇 |
2013年 | 41篇 |
2012年 | 46篇 |
2011年 | 51篇 |
2010年 | 39篇 |
2009年 | 32篇 |
2008年 | 50篇 |
2007年 | 34篇 |
2006年 | 32篇 |
2005年 | 39篇 |
2004年 | 33篇 |
2003年 | 38篇 |
2002年 | 38篇 |
2001年 | 27篇 |
2000年 | 45篇 |
1999年 | 36篇 |
1998年 | 25篇 |
1997年 | 16篇 |
1996年 | 10篇 |
1995年 | 13篇 |
1994年 | 11篇 |
1993年 | 17篇 |
1992年 | 40篇 |
1991年 | 41篇 |
1990年 | 30篇 |
1989年 | 28篇 |
1988年 | 17篇 |
1987年 | 26篇 |
1986年 | 19篇 |
1985年 | 18篇 |
1984年 | 14篇 |
1983年 | 18篇 |
1982年 | 19篇 |
1981年 | 13篇 |
1980年 | 14篇 |
1977年 | 12篇 |
1976年 | 11篇 |
1975年 | 24篇 |
1974年 | 15篇 |
1973年 | 16篇 |
1972年 | 16篇 |
1970年 | 11篇 |
1969年 | 12篇 |
1968年 | 13篇 |
1967年 | 13篇 |
排序方式: 共有1359条查询结果,搜索用时 421 毫秒
991.
992.
Lowe J Drozda S Qian W Peakman MC Liu J Gibbs J Harms J Schmidt C Fisher K Strick C Schmidt A Vanase M Lebel L 《Bioorganic & medicinal chemistry letters》2007,17(6):1675-1678
The synthesis and structure-activity relationships (SAR) of a series of indane and tetralin inhibitors of the type 1 glycine transporter, derived from a high-throughput screening (HTS) hit, are described. Key modifications that reduced the 5HT1B receptor affinity of the HTS hit and the P450 2D6 inhibition of subsequent analogues are delineated. While these modifications led to potent and selective GlyT1 inhibitors, HERG affinity and human microsomal clearance remain an issue for this series of compounds. 相似文献
993.
Dahlhoff EP Fearnley SL Bruce DA Gibbs AG Stoneking R McMillan DM Deiner K Smiley JT Rank NE 《Physiological and biochemical zoology : PBZ》2008,81(6):718-732
Understanding how climate change impacts natural systems requires investigations of the effects of environmental variation on vulnerable species and documentation of how populations respond to change. The willow beetle Chrysomela aeneicollis is ideal for such studies. It lives in California's Sierra Nevada on the southern edge of its worldwide range. Beetles experience elevated air temperatures during summertime egg laying and larval development. Exposure to these temperatures causes physiological stress, which may reduce reproductive success and endanger populations. The glycolytic enzyme phosphoglucose isomerase (PGI) is a marker of temperature adaptation in C. aeneicollis. PGI allele frequency varies across a latitudinal gradient: allele 1 is common in Rock Creek (RC), which is cooler and to the north, and allele 4 is common in Big Pine Creek (BPC), which is warmer and to the south. In populations that are intermediate in geography and climate (e.g., Bishop Creek [BC]), PGI-4 frequency increases from north to south such that alleles 1 and 4 are in relatively equal frequency in southern BC. Over the past decade, Sierra Nevada beetle populations have colonized high elevations and have become extinct at lower elevations where they were once common. In BC, the magnitude of PGI allele frequency fluctuations among life-history stages is related to maximal air temperature, with the frequency of PGI-4 increasing after the hottest part of summer. To identify mechanisms that may cause shifts in PGI allele frequency, we measured metabolic rate and fecundity for beetles collected at BC. Metabolic rate of males and females was measured at 20 degrees and 36 degrees C using flow-through respirometry. To measure laboratory fecundity, mating pairs were acclimated for 4 h each afternoon at a control temperature (20 degrees C) or at mildly elevated temperatures (26 degrees or 32 degrees C) and number of eggs laid was counted daily for 24 d, after which tissue levels of 70-kD heat shock proteins (Hsp70) were determined. Previous studies had demonstrated differences in Hsp70 expression among PGI genotypes at these temperatures. To measure field fecundity, mating pairs from BC were transplanted to similar elevations in BPC, BC, and RC and were monitored in situ for 24 d. Metabolic rate was higher for PGI 4-4 genotypes than for PGI 1-4 or PGI 1-1 individuals at 36 degrees C but not at 20 degrees C. In contrast, laboratory fecundity was greatest for females possessing PGI-1, independent of acclimation temperature. At the end of the laboratory fecundity experiment, Hsp70 expression was positively related to fecundity, suggesting minimal reproductive cost of upregulation of heat shock proteins in response to mild heat stress. In the field, fecundity was highest for PGI 1-1 and PGI 1-4 individuals in RC and PGI 4-4 individuals in BPC and was similar for all genotypes in BC. Thus, fecundity in nature was greatest for the genotypes that were most common in each area. Taken together, data reported here suggest that hot, dry summers in the Sierra Nevada may result in an increase in frequency of the PGI-4 allele and shifts to higher elevations for C. aeneicollis populations. 相似文献
994.
Effect of Lyophilization and Freeze-thawing on the Stability of siRNA-liposome Complexes 总被引:1,自引:0,他引:1
The purpose of this research was to describe the application of lyophilization in the delivery of siRNA using cationic lipids
by addressing the long-term formulation/stability issues associated with cationic lipids and to understand the mechanism of
lyoprotection. siRNA liposomes complexes were formed in different potential cyro/lyoprotectants and subjected to either lyophilization
or freeze thaw cycles. siRNA, liposomes and/or lipoplexes were tested for activity, SYBR Green I binding, cellular uptake
and particle size. The lipoplexes when lyophilized in the presence of sugars as lyoprotectants could be lyophilized and reconstituted
without loss of transfection efficacy but in ionic solutions they lost 65–75% of their functionality. The mechanism of this
loss of activity was further investigated. The lyophilization process did not alter siRNA’s intrinsic biological activity
as was evident by the ability of lyophilized siRNA to retain functionality and SYBR green I binding ability. While the lipoplex
size dramatically increased (∼50–70 times) after lyophilization in the absence of non-ionic lyoprotectants. This increase
in size correlated to the decrease in cellular accumulation of siRNA and a decrease in activity. In conclusion, siRNAs can
be applied in cationic lipid lyophilized formulations and these complexes represent a potential method of increasing the stability
of pre-formed complex. 相似文献
995.
The rat genome project and the resources that it has generated are transforming the translation of rat biology to human medicine. The rat genome was sequenced to a high quality "draft," the structure and location of the genes were predicted, and a global assessment was published (Gibbs RA et al., Nature 428: 493-521, 2004). Since that time, researchers have made use of the genome sequence and annotations and related resources. We take this opportunity to review the currently available rat genome resources and to discuss the progress and future plans for the rat genome. 相似文献
996.
997.
Oligosaccharyltransferase (OST) catalyzes the transfer of a branched oligosaccharide from a dolichylpyrophosphate oligosaccharide (Dol-PP-OS) to the asparagine of a nascent polypeptide chain in vivo and peptide substrates in vitro. Here we report the isolation and purification of Dol-PP-OS from bovine pancreas and thyroid. Steady-state kinetic parameters comparing the two Dol-PP-OS to a shorter dolichylpyrophosphate disaccharide (DolPP-DS) previously synthesized in our laboratory are reported. These were determined for Dol-PP-OS, Dol-PP-DS, and the tripeptide Bz-Asn-Leu-Thr-NH2 with solubilized OST and, for the first time, saturation kinetics were observed for all substrates. The kinetic data provide a basis for analyzing quantitatively the individual contributions of oligosaccharide donor and peptide acceptor substrates to OST-catalyzed glycosylation. 相似文献
998.
T M Ciccarone S C MacTough T M Williams C J Dinsmore T J O'Neill D Shah J C Culberson K S Koblan N E Kohl J B Gibbs A I Oliff S L Graham G D Hartman 《Bioorganic & medicinal chemistry letters》1999,9(14):1991-1996
The design and syntheses of non-thiol inhibitors of farnesyl-protein transferase are described. Substitutions on an imidazolylmethyl-AMBA-methionine template gave a highly potent and cell-active inhibitor. 相似文献
999.
Sarah?A.?Smiley-WaltersEmail author Terence?M.?Farrell H.?Lisle?Gibbs 《Oecologia》2017,184(4):739-748
Theory predicts that predator–prey interactions can generate reciprocal selection pressures on species pairs, which can result in local adaptation, yet the presence and pattern of local adaptation is poorly studied in vertebrate predator–prey systems. Here, we used a reciprocal common garden (laboratory) experimental design involving comparisons between local and foreign populations to determine if local adaptation was present between a generalist predator—the pigmy rattlesnake (Sistrurus miliarius)—and a co-occurring prey—the squirrel treefrog (Hyla squirella). We conducted toxicity trials using snake venom from two populations separated by 340 km tested on prey from sympatric and allopatric populations, resulting in data from four venom origin–frog origin combinations. We assessed venom effectiveness using two measures (frog mortality at 24 h and time to frog death) and then used regression analyses to look for a signal of local adaptation with either measure. We found evidence for local adaptation for one measure (time to death), but not the other (frog mortality). We argue that in this system, the time to death of a prey item is a more ecologically relevant measure of venom effectiveness than is frog mortality at 24 h. Our results document an example of local adaptation between two interacting vertebrates using a whole-organism assay and a local versus foreign criteria and provide evidence that population-level variation in snake venom is adaptive. 相似文献
1000.
Sean R. Griffin Bethanne Bruninga‐Socolar Morgan A. Kerr Jason Gibbs Rachael Winfree 《Restoration Ecology》2017,25(4):650-660
Restoration efforts often focus on plants, but additionally require the establishment and long‐term persistence of diverse groups of nontarget organisms, such as bees, for important ecosystem functions and meeting restoration goals. We investigated long‐term patterns in the response of bees to habitat restoration by sampling bee communities along a 26‐year chronosequence of restored tallgrass prairie in north‐central Illinois, U.S.A. Specifically, we examined how bee communities changed over time since restoration in terms of (1) abundance and richness, (2) community composition, and (3) the two components of beta diversity, one‐to‐one species replacement, and changes in species richness. Bee abundance and raw richness increased with restoration age from the low level of the pre‐restoration (agricultural) sites to the target level of the remnant prairie within the first 2–3 years after restoration, and these high levels were maintained throughout the entire restoration chronosequence. Bee community composition of the youngest restored sites differed from that of prairie remnants, but 5–7 years post‐restoration the community composition of restored prairie converged with that of remnants. Landscape context, particularly nearby wooded land, was found to affect abundance, rarefied richness, and community composition. Partitioning overall beta diversity between sites into species replacement and richness effects revealed that the main driver of community change over time was the gradual accumulation of species, rather than one‐to‐one species replacement. At the spatial and temporal scales we studied, we conclude that prairie restoration efforts targeting plants also successfully restore bee communities. 相似文献