全文获取类型
收费全文 | 6061篇 |
免费 | 465篇 |
国内免费 | 4篇 |
出版年
2023年 | 28篇 |
2022年 | 76篇 |
2021年 | 164篇 |
2020年 | 95篇 |
2019年 | 114篇 |
2018年 | 191篇 |
2017年 | 144篇 |
2016年 | 197篇 |
2015年 | 306篇 |
2014年 | 330篇 |
2013年 | 398篇 |
2012年 | 504篇 |
2011年 | 510篇 |
2010年 | 280篇 |
2009年 | 269篇 |
2008年 | 354篇 |
2007年 | 366篇 |
2006年 | 347篇 |
2005年 | 279篇 |
2004年 | 245篇 |
2003年 | 246篇 |
2002年 | 220篇 |
2001年 | 51篇 |
2000年 | 39篇 |
1999年 | 49篇 |
1998年 | 40篇 |
1997年 | 36篇 |
1996年 | 30篇 |
1995年 | 28篇 |
1994年 | 30篇 |
1993年 | 23篇 |
1992年 | 25篇 |
1991年 | 22篇 |
1990年 | 24篇 |
1989年 | 26篇 |
1988年 | 15篇 |
1987年 | 14篇 |
1986年 | 20篇 |
1985年 | 29篇 |
1984年 | 31篇 |
1983年 | 27篇 |
1982年 | 26篇 |
1981年 | 24篇 |
1980年 | 15篇 |
1979年 | 18篇 |
1978年 | 19篇 |
1977年 | 17篇 |
1976年 | 18篇 |
1974年 | 14篇 |
1973年 | 14篇 |
排序方式: 共有6530条查询结果,搜索用时 288 毫秒
1.
2.
3.
4.
Shreaya Chakroborty Clark Briggs Megan B. Miller Ivan Goussakov Corinne Schneider Joyce Kim Jaime Wicks Jill C. Richardson Vincent Conklin Benjamin G. Cameransi Grace E. Stutzmann 《PloS one》2012,7(12)
Alzheimer’s disease (AD) is a devastating neurodegenerative condition with no known cure. While current therapies target late-stage amyloid formation and cholinergic tone, to date, these strategies have proven ineffective at preventing disease progression. The reasons for this may be varied, and could reflect late intervention, or, that earlier pathogenic mechanisms have been overlooked and permitted to accelerate the disease process. One such example would include synaptic pathology, the disease component strongly associated with cognitive impairment. Dysregulated Ca2+ homeostasis may be one of the critical factors driving synaptic dysfunction. One of the earliest pathophysiological indicators in mutant presenilin (PS) AD mice is increased intracellular Ca2+ signaling, predominantly through the ER-localized inositol triphosphate (IP3) and ryanodine receptors (RyR). In particular, the RyR-mediated Ca2+ upregulation within synaptic compartments is associated with altered synaptic homeostasis and network depression at early (presymptomatic) AD stages. Here, we offer an alternative approach to AD therapeutics by stabilizing early pathogenic mechanisms associated with synaptic abnormalities. We targeted the RyR as a means to prevent disease progression, and sub-chronically treated AD mouse models (4-weeks) with a novel formulation of the RyR inhibitor, dantrolene. Using 2-photon Ca2+ imaging and patch clamp recordings, we demonstrate that dantrolene treatment fully normalizes ER Ca2+ signaling within somatic and dendritic compartments in early and later-stage AD mice in hippocampal slices. Additionally, the elevated RyR2 levels in AD mice are restored to control levels with dantrolene treatment, as are synaptic transmission and synaptic plasticity. Aβ deposition within the cortex and hippocampus is also reduced in dantrolene-treated AD mice. In this study, we highlight the pivotal role of Ca2+ aberrations in AD, and propose a novel strategy to preserve synaptic function, and thereby cognitive function, in early AD patients. 相似文献
5.
We have observed that sperm quality parameters indicative of spermatozoa hyperactivation such are lower “linearity” and “straightness”, and as showed by this research “elongation”, were more pronounced in patients with normal spermiogram compared to the group of men with reduced sperm motility who were undergoing routine in vitro fertilisation. The research encompassed 97 men diagnosed with normozoospermia (n = 20), asthenozoospermia (n = 54) and oligoasthenozoospermia (n = 23). The findings indicate that sperm quality of patients with normal spermiogram diagnosed according to WHO criteria, may be compromised by showing premature spontaneous hyperactivation which can decrease the chances of natural conception. We assessed synergistic effects of multiple chemical elements in ejaculated semen to find if premature spontaneous hyperactivation of spermatozoa can be a sign of imbalanced semen composition especially of elements K, Ca, Cu and Zn. Human semen samples showing low or high baseline status of chemical elements concentrations were found in samples from all three diagnostic groups. However, correlation of K/Ca and Cu/Zn ratios, taking into account samples from all three groups of men, were negative at statistical significance level p = 0.01. We tested if the negative correlation between K/Ca and Cu/Zn ratio works for greater number of semen samples. We found the negative correlation to be valid for 175 semen samples at statistical significance of p = 0.00002. The ratio of K/Ca and Cu/Zn, i.e. increased concentrations of K and Zn in comparison to concentrations of Ca and Cu, were associated with a decrease of “straightness” in the group of men with normal spermiogram and pronounced spontaneous hyperactivation of spermatozoa, implying that these elements act in synergy and that the balance of elements and not their absolute concentrations plays the major role in premature spermatozoa hyperactivation in ejaculated semen. 相似文献
6.
Methyl 3-azido-2-O-benzoyl-3,4-dideoxy-β-dl-erythro-pentopyranoside (6) was synthesized through two routes in five steps from methyl 2,3-anhydro-4-deoxy-β-dl-erythro-pentopyranoside (1). The first route proceeded via selective azide displacement of the 3-tosyloxy group of methyl 4-deoxy-2,3-di-O-tosyl-α-dl-threo-pentopyranoside, followed by detosylation and benzoylation. The second route consisted, with a better overall yield, in the azide displacement of the mesyloxy group of methyl O-benzoyl-4-deoxy-3-O-methylsulfonyl-α-dl-threo-pentopyranoside (10), obtained by benzylate opening of 1, followed by benzoylation, debenzylation, and mesylation. Compound 6 was transformed into its glycosyl chloride, further treated by 6-chloropurine to give the nucleoside 9-(3-azido-2-O-benzoyl-3,4-dideoxy-β-dl-erythro-pentopyranosyl)-6-chloropurine (13). When treated with propanolic ammonia, 13 yielded 9-(3-azido-3,4-dideoxy-β-dl-erythro-pentopyranosyl)adenine. 相似文献
7.
8.
9.
Patricia Pacheco Daniel J. Crawford Tod F. Stuessy Mario Silva O. 《American journal of botany》1991,78(4):534-543
Leaf flavonoid chemistry was examined from the three subgenera and 11 species of the endemic genus Dendroseris (Compositae, Lactuceae) of the Juan Fernandez Islands, Chile. Eight of the species are restricted to the older island (Masatierra, ca. 4 million years old), which is also closer to the mainland. Three species, one from each subgenus, are restricted to Masafuera, which is younger geologically (1–2 million years old) and 145 km further west of Masatierra. A total of 16 compounds was identified, with the 7-0-glucosides of the flavones apigenin and luteolin accounting for 12 of the constituents. Two glucosides of the flavonol quercetin were detected. Despite considerable interpopulation variation within species, six of the taxa have distinctive flavonoid profiles. Although there are few absolute differences among the subgenera, they can be distinguished chemically. Subgenus Rea contains the greatest number of compounds, and a previous cladistic analysis based on morphological features suggested this subgenus as most primitive. Subgenus Phoenicoseris is considered highly derived morphologically, and it has a reduced flavonoid chemistry. Very little reduction in flavonoid diversity was seen in the morphologically specialized subg. Dendroseris as compared to subg. Rea. A trend in reduction of numbers of compounds was seen for two of the three species on the younger island of Masafuera when compared to their presumed ancestors on Masatierra. Flavonoids of selected species of Hieracium and Hypochaeris, presumptive mainland progenitors of Dendroseris, reveal a close chemical affinity with the former genus. 相似文献
10.
Inhibition of growth of Leishmania mexicana mexicana by Leishmania mexicana amazonensis during "in vitro" co-cultivation 总被引:1,自引:0,他引:1
Inhibition of one Leishmania subspecies by exometabolites of another subspecies, a phenomenon not previously reported, is suggested by our recent observations in cell cloning experiments with Leishmania mexicana mexicana and Leishmania mexicana amazonensis. Clones were identified using the technique of schizodeme analysis. The phenomenon observed is clearly relevant to studies of parasite isolation, leishmanial metabolism, cross-immunity and chemotherapy. 相似文献