全文获取类型
收费全文 | 4407篇 |
免费 | 318篇 |
国内免费 | 2篇 |
出版年
2023年 | 18篇 |
2022年 | 38篇 |
2021年 | 78篇 |
2020年 | 35篇 |
2019年 | 52篇 |
2018年 | 105篇 |
2017年 | 101篇 |
2016年 | 154篇 |
2015年 | 211篇 |
2014年 | 217篇 |
2013年 | 276篇 |
2012年 | 322篇 |
2011年 | 322篇 |
2010年 | 223篇 |
2009年 | 193篇 |
2008年 | 226篇 |
2007年 | 249篇 |
2006年 | 207篇 |
2005年 | 198篇 |
2004年 | 179篇 |
2003年 | 135篇 |
2002年 | 139篇 |
2001年 | 109篇 |
2000年 | 63篇 |
1999年 | 58篇 |
1998年 | 45篇 |
1997年 | 24篇 |
1996年 | 30篇 |
1995年 | 32篇 |
1994年 | 26篇 |
1993年 | 25篇 |
1992年 | 40篇 |
1991年 | 25篇 |
1990年 | 37篇 |
1989年 | 36篇 |
1988年 | 27篇 |
1987年 | 36篇 |
1986年 | 19篇 |
1985年 | 22篇 |
1984年 | 24篇 |
1983年 | 21篇 |
1982年 | 19篇 |
1981年 | 19篇 |
1977年 | 21篇 |
1976年 | 22篇 |
1975年 | 27篇 |
1974年 | 19篇 |
1973年 | 20篇 |
1971年 | 17篇 |
1966年 | 17篇 |
排序方式: 共有4727条查询结果,搜索用时 31 毫秒
141.
Béatrice Heurtault Jean-Sébastien Thomann Justyna Jedrzejewska Winfried S. Wels Francis Schuber Benoît Frisch 《Journal of liposome research》2013,23(3):205-213
We have developed liposome-based synthetic constructs incorporating peptide epitope(s) (ErbB2 p63-67 CTL which is overexpressed in many tumors and/or HA 307-319 T-helper) and lipopeptide adjuvants (Pam3CysSerSer, Pam3CysAlaGly) in order to elicit an anti-tumor immune response. The epitopes, derivatized with a linker containing a cysteine residue, were conjugated on preformed vesicles (dia. ~ 100 nm) containing lipopeptides functionalized with thiol reactive groups (maleimide or bromoacetyl). The therapeutic efficacy of these constructs was evaluated on a Balb/c mice tumor model inoculated with syngenic murine renal carcinoma (Renca) cells expressing human ErbB2 (Her2/neu) receptor. A successful therapeutic vaccination was obtained which was antigen specific. Furthermore, it appeared that the nature of the polar head group of the lipopeptide adjuvant and also its type of functionalization influence the efficacy of the construct. In our study, the best results were obtained with formulations containing a Pam3CSS anchor in association with the CTL and Th epitopes. Considering these promising results studies are in progress with a new generation of liposomes that incorporate a neutral lipid – lacking adjuvant properties – that serves as anchor of the peptide epitopes and new adjuvants synthesized in our laboratory, which are screened for their antitumour activity in a therapeutic setting. 相似文献
142.
Marianne Rooman Emilie Cauët Jacques Liévin René Wintjens 《Journal of biomolecular structure & dynamics》2013,31(6):949-954
Abstract Electron holes are known to migrate along the DNA or RNA duplexes and to localize preferentially on successive guanines. The stationary point conformations of Gua pairs that can trap or let pass these holes have been characterized by quantum chemistry calculations. Here we show their recurrent occurrence in DNA and RNA X-ray structures, often in quadruplex conformations or in interaction with proteins, ligands or metal ions. These findings give support to the biological, possibly regulatory, roles of charge migration in cell functioning. 相似文献
143.
Abstract The thermally stimulated depolarization current (TSDC) measurements in frozen aqueous solutions, gels and solid layers of NaDNA show typically up to three dipolar overlapping peaks in the low-temperature range of 80—;150 K. Up to four discrete relaxation peaks have been observed at higher temperatures above 150 K. The low-temperature TSDC peaks are due to the dipolar relaxations of free and loosely bound water which crystallizes. Part of bound water especially in the first hydration shell of DNA molecule is at low temperatures in the form of glass. The transition of this glass from solidlike behavior to liquidlike behavior observed mainly in gels and solid samples is associated with a previously founded TSDC relaxation peak. The peak is at its maximum at 165- 250 K depending on the sample humidity. Existence of this relaxation in the samples with water contents in a broad range confirms, that the slowly relaxing shell (minimally 5–7 water molecules/nucleotide) closely associated with DNA double helix retains its characteristics. Also another peak of the high-temperature band at 180–205 K which was observed in the samples at hydration 2–1800 g H2O/g dry NaDNA is due to a relaxation in the sample volume. At the highest temperatures relax the space charges trapped at the electrodes. 相似文献
144.
Ivan Barvík Jr. Josef Štěpánek Jiří Bok 《Journal of biomolecular structure & dynamics》2013,31(5):863-875
Abstract Impact of the internucleoside linkage modification by inserting a methylene group on the ability of the modified oligonucleotide to hybridize with a natural DNA strand was studied by fully solvated molecular dynamics (MD) simulations. Three undecamer complexes were analyzed: natural dT11.dA11 duplex as a reference and two its analogs with alternating modified and natural linkages in the deoxyadenosine chain. The isopolar, non-isosteric modified linkages were of 5′-O-PO2-CH2-O-3′ (5′PC3′) or 5′-O-CH2-PO2-O-3′ (5′CP3′) type. Simulations were performed by using the AMBER 5.0 software package with the force field completed by a set of parameters needed to model the modified segments. Both modifications were found to lead to double helical complexes, in which the thymidine strand as well as deoxyriboses and unmodified linkages in the adenosine strand adopted conformations typical for the B-type structure. For each of the two conformational richer modified linkages two stable conformations were found at 300 K: the -ggt and ggt for the 5′PC3′ and ggg, tgg for the 5′CP3′, respectively. Both modified chains adopted helical conformations with heightened values of the inclination parameter but without affecting the Watson-Crick hydrogen bonds. 相似文献
145.
146.
Isabelle Côté 《Ethnic and racial studies》2013,36(11):1855-1873
The tumultuous events of summer 2009 have brought Uighur protests and minority mobilization in the Xinjiang Uighur Autonomous Region (XUAR) to the forefront. But this focus overlooks similar protests organized by various groups of Han Chinese settlers over the years. This paper contributes to the body of literature on minority mobilization and ethnic relations in Xinjiang by illustrating how the political mobilization of a group that is simultaneously a national majority and a regional minority differs substantially from ‘traditional’ minority mobilization. Reviewing the main instances of Han Chinese political mobilization since the XUAR was created in 1955, I argue that two factors are particularly important in enabling their mobilization: the Han Chinese's subjective perception of discrimination and their close ethnic ties to the state. This paper concludes with a discussion on the presence of a cycle of protests between Han settlers and the Uighurs in Xinjiang. 相似文献
147.
Yashar Feyziyev Zsuzsanna Deák Stenbjörn Styring Gábor Bernát 《Journal of bioenergetics and biomembranes》2013,45(1-2):111-120
The Mn4CaO5 cluster of photosystem II (PSII) catalyzes the oxidation of water to molecular oxygen through the light-driven redox S-cycle. The water oxidizing complex (WOC) forms a triad with TyrosineZ and P680, which mediates electrons from water towards the acceptor side of PSII. Under certain conditions two other redox-active components, TyrosineD (YD) and Cytochrome b 559 (Cyt b 559) can also interact with the S-states. In the present work we investigate the electron transfer from Cyt b 559 and YD to the S2 and S3 states at 195 K. First, YD ? and Cyt b 559 were chemically reduced. The S2 and S3 states were then achieved by application of one or two laser flashes, respectively, on samples stabilized in the S1 state. EPR signals of the WOC (the S2-state multiline signal, ML-S2), YD ? and oxidized Cyt b 559 were simultaneously detected during a prolonged dark incubation at 195 K. During 163 days of incubation a large fraction of the S2 population decayed to S1 in the S2 samples by following a single exponential decay. Differently, S3 samples showed an initial increase in the ML-S2 intensity (due to S3 to S2 conversion) and a subsequent slow decay due to S2 to S1 conversion. In both cases, only a minor oxidation of YD was observed. In contrast, the signal intensity of the oxidized Cyt b 559 showed a two-fold increase in both the S2 and S3 samples. The electron donation from Cyt b 559 was much more efficient to the S2 state than to the S3 state. 相似文献
148.
Sally E. Thomas Elke Malzer Adriana Ordó?ez Lucy E. Dalton Emily F. A. van ′t Wout Elizabeth Liniker Damian C. Crowther David A. Lomas Stefan J. Marciniak 《The Journal of biological chemistry》2013,288(11):7606-7617
Cell cycle checkpoints ensure that proliferation occurs only under permissive conditions, but their role in linking nutrient availability to cell division is incompletely understood. Protein folding within the endoplasmic reticulum (ER) is exquisitely sensitive to energy supply and amino acid sources because deficiencies impair luminal protein folding and consequently trigger ER stress signaling. Following ER stress, many cell types arrest within the G1 phase, although recent studies have identified a novel ER stress G2 checkpoint. Here, we report that ER stress affects cell cycle progression via two classes of signal: an early inhibition of protein synthesis leading to G2 delay involving CHK1 and a later induction of G1 arrest associated both with the induction of p53 target genes and loss of cyclin D1. We show that substitution of p53/47 for p53 impairs the ER stress G1 checkpoint, attenuates the recovery of protein translation, and impairs induction of NOXA, a mediator of cell death. We propose that cell cycle regulation in response to ER stress comprises redundant pathways invoked sequentially first to impair G2 progression prior to ultimate G1 arrest. 相似文献
149.
Caroline Richard Patrick Couture Sophie Desroches Alice H. Lichtenstein Beno?t Lamarche 《Journal of lipid research》2013,54(1):232-237
We investigated the effect of weight loss, independent of change in diet composition, on HDL and apoAI metabolism in men with metabolic syndrome (MetS). Subjects (19 men with MetS [NCEP-ATPIII]) were fed an isoenergetic Mediterranean-style diet for 5 weeks (all foods provided). Participants then underwent a 20-week free-living period during which they were counseled to restrict energy intake, after which they were again fed an isoenergetic Mediterranean-style diet for 5 weeks. At the end of the two controlled diets, participants received a single bolus of [5,5,5-2H3] L-leucine, and fasting blood samples were collected over a 96 h period. ApoAI kinetic was assessed using multicompartmental modeling of the tracer enrichment data. Participants achieved a 9.1 ± 2.8% reduction in body weight (P < 0.001). Weight loss resulted in an increase in plasma HDL-cholesterol (HDL-C) concentrations of 6.0% (P = 0.059) and HDL3-C of 7.9% (P = 0.045), attributable to a reduction in apoAI fractional catabolic rate (−7.8%; P = 0.046) with no change in apoAI production rate (2.2%; P = 0.58). These data indicate that weight loss, independent of variation in diet composition, increases plasma HDL primarily by delaying the catabolism of apoAI. 相似文献
150.