全文获取类型
收费全文 | 1116篇 |
免费 | 111篇 |
专业分类
1227篇 |
出版年
2022年 | 9篇 |
2021年 | 16篇 |
2020年 | 17篇 |
2019年 | 15篇 |
2018年 | 20篇 |
2017年 | 21篇 |
2016年 | 18篇 |
2015年 | 42篇 |
2014年 | 34篇 |
2013年 | 53篇 |
2012年 | 55篇 |
2011年 | 61篇 |
2010年 | 42篇 |
2009年 | 38篇 |
2008年 | 58篇 |
2007年 | 59篇 |
2006年 | 46篇 |
2005年 | 42篇 |
2004年 | 60篇 |
2003年 | 50篇 |
2002年 | 36篇 |
2001年 | 40篇 |
2000年 | 27篇 |
1999年 | 40篇 |
1998年 | 14篇 |
1997年 | 18篇 |
1996年 | 14篇 |
1995年 | 14篇 |
1994年 | 14篇 |
1993年 | 10篇 |
1992年 | 18篇 |
1991年 | 17篇 |
1990年 | 16篇 |
1989年 | 18篇 |
1988年 | 20篇 |
1987年 | 13篇 |
1986年 | 13篇 |
1985年 | 11篇 |
1983年 | 5篇 |
1982年 | 9篇 |
1981年 | 7篇 |
1979年 | 10篇 |
1978年 | 8篇 |
1977年 | 7篇 |
1976年 | 6篇 |
1975年 | 7篇 |
1974年 | 7篇 |
1973年 | 7篇 |
1971年 | 7篇 |
1970年 | 5篇 |
排序方式: 共有1227条查询结果,搜索用时 15 毫秒
991.
Pyridazinones as selective cyclooxygenase-2 inhibitors 总被引:4,自引:0,他引:4
Li CS Brideau C Chan CC Savoie C Claveau D Charleson S Gordon R Greig G Gauthier JY Lau CK Riendeau D Thérien M Wong E Prasit P 《Bioorganic & medicinal chemistry letters》2003,13(4):597-600
Pyridazinone was found to be an excellent core template for selective COX-2 inhibitors. Two potent, selective and orally active COX-2 inhibitors, which were highly efficacious in rat paw edema and rat pyresis models, have been obtained. 相似文献
992.
Wang B Baldassarre H Tao T Gauthier M Neveu N Zhou JF Leduc M Duguay F Bilodeau AS Lazaris A Keefer C Karatzas CN 《Molecular reproduction and development》2002,63(4):437-443
This study was undertaken to investigate various factors affecting the outcomes of in vitro fertilization (IVF) of oocytes retrieved by laparoscopic ovum pick-up (LOPU) technique from prepubertal and adult goats, as well as to evaluate the developmental competence of in vitro produced embryos. Oocyte-cumulus complexes recovered by LOPU from donors stimulated with gonadotrophins were matured in vitro. Fresh semen was used for IVF following various capacitation treatments. In vitro produced zygotes were either cultured to assess in vitro development or were transferred into recipients for full term development. The results indicated that successful IVF of the goat oocytes was affected by factors such as sperm capacitation treatment, oocyte quality, and abundance of cumulus cells on zona pellucida. Oocytes from both prepubertal and adult goats demonstrated similar full term developmental competence despite the fact that in vitro developmental rates were lower for prepubertal goats. The births of transgenic offspring demonstrated that the established LOPU-IVF technology combined with pronuclear microinjection can be successfully used to produce transgenic goats. 相似文献
993.
Despite numerous studies on breeding dispersal, it is still unclear how habitat heterogeneity and previous nesting success
interact to determine nest-site fidelity at various spatial scales. In this context, we investigated factors affecting breeding
dispersal in greater snow geese (Anser caerulescens atlanticus), an Arctic breeding species nesting in two contrasting habitats (wetlands and mesic tundra) with variable pattern of snowmelt
at the time of settlement in spring. From 1994 to 2005, we monitored the nesting success and breeding dispersal of individually
marked females. We found that snow geese showed a moderate amount of nest-site fidelity and considerable individual variability
in dispersal distance over consecutive nesting attempts. This variability can be partly accounted for by the annual timing
of snowmelt. Despite this environmental constraint, habitat differences at the colony level consistently affected nesting
success and settlement patterns. Females nesting in wetlands had higher nesting success than those nesting in mesic tundra.
Moreover, geese responded adaptively to spatial heterogeneity by showing fidelity to their nesting habitat, independently
of snowmelt pattern. From year to year, geese were more likely to move from mesic to high-quality wetland habitat, regardless
of previous nesting success and without cost on their subsequent nesting performance. The unpredictability of snowmelt and
the low cost of changing site apparently favour breeding-site dispersal although habitat quality promotes fidelity at the
scale of habitat patches. 相似文献
994.
F Lecaille J Cotton J H McKerrow M Ferrer-Di Martino E Boll-Bataillé F Gauthier G Lalmanach 《FEBS letters》2001,507(3):362-366
A library of 121 pseudopeptides was designed to develop reversible inhibitors of trypanosomal enzymes (cruzain from Trypanosoma cruzi and congopain from Trypanosoma congolense). The peptides share the framework: Cha-X1-X2-Pro (Cha=cyclohexyl-alanine, X1 and X2 were phenylalanyl analogs), based on a previous report [Lecaille, F., Authié, E., Moreau, T., Serveau, C., Gauthier, F. and Lalmanach, G. (2001) Eur. J. Biochem. 268, 2733-2741]. Five peptides containing a nitro-substituted aromatic residue (Tyr/Phe) and one a 4-chloro-phenylalanine at the X1 position, and 3-(2-naphthyl)-alanine, homocyclohexylalanine or 3-nitro-tyrosine (3-NO(2)-Tyr) at the X2 position, were selected. They inhibited congopain more effectively than cruzain, except Cha-4-NO(2)-Phe-3-NO(2)-Tyr-Pro which bound the two parasitic enzymes similarly. Among this series, Cha-3-NO(2)-Tyr-HoCha-Pro and Cha-4-NO(2)-Phe-3-NO(2)-Tyr-Pro are the most selective for congopain relative to host cathepsins. No hydrolysis occurred upon prolonged incubation time with purified enzymes. In addition introduction of non-proteogenic residues in the peptidyl backbone greatly enhanced resistance to proteolysis by mammalian sera. 相似文献
995.
Philip Awadalla Julie Gauthier Rachel A. Myers Ferran Casals Alexander R. Griffing Edouard Henrion Julien Tarabeux Yan Yang Carlos Bustamante Judith L. Rapoport J. Lynn E. DeLisi Ridha Joober Éric Fombonne Martine Zilversmit Hussein Daoud Marie-Hélène Roy-Gagnon Adam Eyre-Walker Eric A. Stone Guy A. Rouleau 《American journal of human genetics》2010,87(3):316-324
The role of de novo mutations (DNMs) in common diseases remains largely unknown. Nonetheless, the rate of de novo deleterious mutations and the strength of selection against de novo mutations are critical to understanding the genetic architecture of a disease. Discovery of high-impact DNMs requires substantial high-resolution interrogation of partial or complete genomes of families via resequencing. We hypothesized that deleterious DNMs may play a role in cases of autism spectrum disorders (ASD) and schizophrenia (SCZ), two etiologically heterogeneous disorders with significantly reduced reproductive fitness. We present a direct measure of the de novo mutation rate (μ) and selective constraints from DNMs estimated from a deep resequencing data set generated from a large cohort of ASD and SCZ cases (n = 285) and population control individuals (n = 285) with available parental DNA. A survey of ∼430 Mb of DNA from 401 synapse-expressed genes across all cases and 25 Mb of DNA in controls found 28 candidate DNMs, 13 of which were cell line artifacts. Our calculated direct neutral mutation rate (1.36 × 10−8) is similar to previous indirect estimates, but we observed a significant excess of potentially deleterious DNMs in ASD and SCZ individuals. Our results emphasize the importance of DNMs as genetic mechanisms in ASD and SCZ and the limitations of using DNA from archived cell lines to identify functional variants. 相似文献
996.
997.
Bukhari IA Shah AJ Gauthier KM Walsh KA Koduru SR Imig JD Falck JR Campbell WB 《American journal of physiology. Heart and circulatory physiology》2012,302(8):H1574-H1583
Arachidonic acid is metabolized to four regioisomeric epoxyeicosatrienoic acids (EETs) by cytochrome P-450. 5,6-, 8,9-, 11,12-, and 14,15-EET are equipotent in relaxing bovine coronary arteries (BCAs). Vasorelaxant effects of EETs are nonselectively antagonized by 14,15-epoxyeicosa-5(Z)-enoic acid. The 11,12-EET analogs, 20-hydroxy-11,12-epoxyeicosa-8(Z)-enoic acid (20-H-11,12-EE8ZE) and 11,12,20-trihydroxyeicosa-8(Z)-enoic acid (11,12,20-THE8ZE) were synthesized and tested for antagonist activity against EET-induced relaxations in BCAs. In U-46619-preconstricted arterial rings, 5,6-, 8,9-, 11,12-, and 14,15-EET caused concentration-dependent relaxations with maximal relaxations ranging from 80 to 96%. Preincubation of arteries with 20-H-11,12-EE8ZE (10(-5) M) inhibited relaxations to 14,15- and 11,12-EET, but not 5,6- and 8,9-EET; however, greatest inhibitory effect was against 11,12-EET (maximal relaxation = 80.6 ± 4.6 vs. 26.7 ± 7.4% without and with 20-H-11,12-EE8ZE, respectively). Preincubation with the soluble epoxide hydrolase inhibitor (tAUCB, 10(-6) M) significantly enhanced the antagonist effect of 20-H-11,12-EE8ZE against 14,15-EET-induced relaxations (maximal relaxation = 86.6 ± 4.4 vs. 27.8 ± 3.3%, without and with 20-H-11,12-EE8ZE and tAUCB) without any change in its effect against 11,12-EET-induced relaxations. In contrast to the parent compound, the metabolite, 11,12,20-THE8ZE (10(-5) M), significantly inhibited relaxations to 11,12-EET and was without effect on other EET regioisomers. Mass spectrometric analysis revealed conversion of 20-H-11,12-EE8ZE to 11,12,20-THE8ZE by incubation with BCA. The conversion was blocked by tAUCB. 14,15-Dihydroxy-eicosa-5Z-enoic acid (a 14,15-EET antagonist), but not 11,12,20-THE8ZE (an 11,12-EET antagonist), inhibited BCA relaxations to arachidonic acid and flow-induced dilation in rat mesenteric arteries. These results indicate that 11,12,20-THE8ZE is a selective antagonist of 11,12-EET relaxations and a useful pharmacological tool to elucidate the function of 11,12-EET in the cardiovascular system. 相似文献
998.
999.
Destruction of lysine by nonreducing sugars 总被引:1,自引:0,他引:1
1000.
Souissi N Bessot N Chamari K Gauthier A Sesboüé B Davenne D 《Chronobiology international》2007,24(4):739-748
The purpose of this study was to evaluate the effects of time of day on aerobic contribution during high-intensity exercise. A group of 11 male physical education students performed a Wingate test against a resistance of 0.087 kg . kg(-1) body mass. Two different times of day were chosen, corresponding to the minimum (06:00 h) and the maximum (18:00 h) levels of power. Oxygen uptake (.VO(2)) was recorded breath by breath during the test (30 sec). Blood lactate concentrations were measured at rest, just after the Wingate test, and again 5 min later. Oral temperature was measured before each test and on six separate occasions at 02:00, 06:00, 10:00, 14:00, 18:00, and 22:00 h. A significant circadian rhythm was found in body temperature with a circadian acrophase at 18:16+/-00:25 h as determined by cosinor analysis. Peak power (P(peak)), mean power (P(mean)), total work done, and .VO(2) increased significantly from morning to afternoon during the Wingate Test. As a consequence, aerobic contribution recorded during the test increased from morning to afternoon. However, no difference in blood lactate concentrations was observed from morning to afternoon. Furthermore, power decrease was greater in the morning than afternoon. Altogether, these results indicate that the time-of-day effect on performances during the Wingate test is mainly due to better aerobic participation in energy production during the test in the afternoon than in the morning. 相似文献