全文获取类型
收费全文 | 4203篇 |
免费 | 345篇 |
国内免费 | 2篇 |
专业分类
4550篇 |
出版年
2023年 | 24篇 |
2022年 | 60篇 |
2021年 | 108篇 |
2020年 | 56篇 |
2019年 | 74篇 |
2018年 | 116篇 |
2017年 | 85篇 |
2016年 | 152篇 |
2015年 | 200篇 |
2014年 | 246篇 |
2013年 | 321篇 |
2012年 | 393篇 |
2011年 | 338篇 |
2010年 | 226篇 |
2009年 | 187篇 |
2008年 | 244篇 |
2007年 | 222篇 |
2006年 | 197篇 |
2005年 | 189篇 |
2004年 | 172篇 |
2003年 | 150篇 |
2002年 | 144篇 |
2001年 | 32篇 |
2000年 | 29篇 |
1999年 | 35篇 |
1998年 | 48篇 |
1997年 | 19篇 |
1996年 | 25篇 |
1995年 | 22篇 |
1994年 | 22篇 |
1993年 | 18篇 |
1992年 | 23篇 |
1991年 | 18篇 |
1990年 | 25篇 |
1989年 | 19篇 |
1988年 | 16篇 |
1987年 | 15篇 |
1985年 | 11篇 |
1984年 | 25篇 |
1983年 | 14篇 |
1982年 | 17篇 |
1981年 | 16篇 |
1980年 | 19篇 |
1979年 | 17篇 |
1978年 | 16篇 |
1977年 | 8篇 |
1973年 | 7篇 |
1969年 | 7篇 |
1964年 | 7篇 |
1962年 | 7篇 |
排序方式: 共有4550条查询结果,搜索用时 0 毫秒
111.
Irene Friligou Evangelia Papadimitriou Dimitrios Gatos John Matsoukas Theodore Tselios 《Amino acids》2011,40(5):1431-1440
A fast and efficient microwave-assisted solid phase peptide synthesis (MW-SPPS) of a 51mer peptide, the main heparin-binding
site (60–110) of human pleiotrophin (hPTN), using 2-chlorotrityl chloride resin (CLTR-Cl) following the 9-fluorenylmethyloxycarbonyl/tert-butyl (Fmoc/tBu) methodology and with the standard N,N′-diisopropylcarbodiimide/1-hydroxybenzotriazole (DIC/HOBt) coupling reagents, is described. An MW-SPPS protocol was for the
first time successfully applied to the acid labile CLTR-Cl for the faster synthesis of long peptides (51mer peptide) and with
an enhanced purity in comparison to conventional SPPS protocols. The synthesis of such long peptides is not trivial and it
is generally achieved by recombinant techniques. The desired linear peptide was obtained in only 30 h of total processing
time and in 51% crude yield, in which 60% was the purified product obtained with 99.4% purity. The synthesized peptide was
purified by reversed phase high performance liquid chromatography (RP-HPLC) and identified by electrospray ionization mass
spectrometry (ESI-MS). Then, the regioselective formation of the two disulfide bridges of hPTN 60–110 was successfully achieved
by a two-step procedure, involving an oxidative folding step in dimethylsulfoxide (DMSO) to form the Cys77–Cys109 bond, followed by iodine oxidation to form the Cys67–Cys99 bond. 相似文献
112.
113.
Irene Litosch 《Biochemical and biophysical research communications》2009,390(3):603-960
Phosphatidic acid (PA) is interactive with Gαq-linked agonists to stimulate GPCR signaling via phospholipase C-β1 (PLC-β1). Phorbol 12-myristate 13-acetate (PMA) increases cellular levels of PA and phospholipase D activity (PLD). This study evaluated whether PMA can stimulate PLC-β1 activity via PA, independent of GPCR input in transfected COS 7 cells. PMA alone had little effect on PLC activity in cells co-transfected with PLC-β1 and Gαq. Activated Gαq, induced by co-transfecting muscarinic cholinergic receptor (m1R), was necessary for stimulation of PLC-β1 activity by PMA. Stimulation by PMA was dependent on the PA-regulatory motif of PLC-β1 implicating PA in this mechanism. PLD1 knockdown by antisense decreased responsiveness of PLC-β1 to both PMA and carbachol. PA alone thus has little effect on PLC-β1 activity, but PA and PLD1 synergize with activated Gαq to stimulate PLC-β1 signaling. Coordinate interaction with activated Gαq may serve as an important mechanism to fine tune response to ligands while preventing spurious initiation of PLC-β signaling by PA in cells. 相似文献
114.
Villaseñor IM Cariño FA 《Zeitschrift für Naturforschung. C, Journal of biosciences》2011,66(9-10):441-446
The crude methanol extract of Jatropha curcas leaves exhibited activity against Staphylococcus aureus, Bacillus subtilis, Mycobacterium phlei, Candida albicans, and Trichophyton mentagrophytes but was inactive against Escherichia coli, Pseudomonas aeruginosa, and Saccharomyces cerevisiae. In a bioassay-directed fractionation, two new phorbins were isolated and analysed by spectroscopic methods. Isolate 1 was characterized as an analogue of pheophytin b with a phytyl moiety containing three double bonds which are at positions P2/P3, P6/P7, and P10/P11. Compound 2 was characterized as methyl pheophorbide a with 132-OH and 17- and 17(1)-CH3 moieties. It is active against Serratia marcescens. 相似文献
115.
Sternfeld L Krause E Schmid A Anderie I Latas A Al-Shaldi H Köhl A Evers K Hofer HW Schulz I 《Cellular signalling》2005,17(8):951-960
This study investigates the role of tyrosine phosphorylation and dephosphorylation in the regulation of the Ca(2+) permeant TRPV6 channel. HEK293 cells co-transfected with TRPV6 and the tyrosine phosphatase PTP1B show a constitutive Ca(2+) entry which was independent of tyrosine phosphorylation under resting conditions. Following depletion of intracellular Ca(2+) stores, TRPV6-mediated Ca(2+) entry could be increased in the presence of a tyrosine phosphatase inhibitor (bis-(N,N-dimethyl-hydroxamido) hydroxo-vanadate; DMHV). Inhibition of Src-kinases completely abolished DMHV-induced increase in TRPV6-mediated Ca(2+) influx. Co-transfection with Src led to tyrosine phosphorylation of TRPV6 which could be dephosphorylated by PTP1B. In vivo interaction of TRPV6 with PTP1B was visualized using the bimolecular fluorescence complementation (BiFC) method and proved by co-immunoprecipitation of both proteins. These data indicate that tyrosine phosphorylation is involved in the regulation of the TRPV6 channel protein. 相似文献
116.
Felipe Couñago Ana Aurora Díaz Gavela Gemma Sancho Irene Ortiz Francisco José Marcos Manuel Recio Julio Fernández Raquel Cano Mar Jiménez Israel J. Thuissard David Sanz-Rosa Juan Castro Nováis Eduardo Pardo Yolanda Molina Hugo Pérez García Elia del Cerro 《Reports of Practical Oncology and Radiotherapy》2019,24(5):472-480
AimTo analyse the efficacy and toxicity of postprostatectomy SRT in patients with a BCR evaluated with mpMRI.BackgroundMultiparametric magnetic resonance imaging (mpMRI) has the ability to detect the site of pelvic recurrence in patients with biochemical recurrence (BCR) after radical prostatectomy (RP). However, we do not know the oncological outcomes of mpMRI-guided savage radiotherapy (SRT).ResultsLocal, lymph node, and pelvic bone recurrence was observed in 13, 4 and 2 patients, respectively. PSA levels were significantly lower in patients with negative mpMRI (0.4 ng/mL [0.4]) vs. positive mpMRI (2.2 ng/mL [4.1], p = 0.003). Median planning target volume doses in patients with visible vs. non-visible recurrences were 76 Gy vs. 70 Gy. Overall, mean follow-up was 41 months (6–81). Biochemical relapse-free survival (bRFS) at 3 years was 82.3% and 82.5%, respectively, for the negative and positive mpMRI groups (p = 0.800). Three-year rates of late grade ≥2 urinary and rectal toxicity were 14.8% and 1.9%, respectively; all but one patient recovered without sequelae.ConclusionSRT to the macroscopic recurrence identified by mpMRI is a feasible and well-tolerated option. In this study, there were no differences in bRFS between MRI-positive and MRI-negative patients, indicating effective targeting of MRI-positive lesions. 相似文献
117.
Lupi A Messana I Denotti G Schininà ME Gambarini G Fadda MB Vitali A Cabras T Piras V Patamia M Cordaro M Giardina B Castagnola M 《Proteomics》2003,3(4):461-467
Human salivary cystatins, five major (S, S1, S2, SA, SN) and two minor (C and D), are multifunctional proteins playing a different role in the oral environment. Salivary cystatin SN is able to effectively inhibit lysosomal cathepsins B, C, H and L and cystatin SA inhibits cathepsins C and L in vitro. These activities suggest, particularly for cystatin SN, an important role in the control of proteolytic events in vivo. Differently, cystatins S are involved, together with statherin, in the mineral balance of the tooth. Due to their distinct role, a reliable method for identification and quantification of the different cystatins, as well as of possible truncated and derived forms, could be helpful for the assessment of the status of the oral cavity. To this purpose high-performance liquid chromatography electrospray ionization mass spectrometry (HPLC-ESI MS) was applied to the analysis of human saliva obtained from healthy subjects. All known salivary cystatins, with the exception of cystatin C, were detected. Strong evidence was also obtained for the presence in saliva of post-translational modified isoforms of cystatins, which may be related to donor habits. Cystatin SN and cystatins S, S1 and S2 were well separated by HPLC-ESI MS coupling from other components and thus this approach can be successfully applied to their quantification. 相似文献
118.
119.
The amount and architecture of vigilance states are governed by two distinct processes, which occur at different time scales. The first, a slow one, is related to a wake/sleep dependent homeostatic Process S, which occurs on a time scale of hours, and is reflected in the dynamics of NREM sleep EEG slow-wave activity. The second, a fast one, is manifested in a regular alternation of two sleep states – NREM and REM sleep, which occur, in rodents, on a time scale of ∼5–10 minutes. Neither the mechanisms underlying the time constants of these two processes – the slow one and the fast one, nor their functional significance are understood. Notably, both processes are primarily apparent during sleep, while their potential manifestation during wakefulness is obscured by ongoing behaviour. Here, we find, in mice provided with running wheels, that the two sleep processes become clearly apparent also during waking at the level of behavior and brain activity. Specifically, the slow process was manifested in the total duration of waking periods starting from dark onset, while the fast process was apparent in a regular occurrence of running bouts during the waking periods. The dynamics of both processes were stable within individual animals, but showed large interindividual variability. Importantly, the two processes were not independent: the periodic structure of waking behaviour (fast process) appeared to be a strong predictor of the capacity to sustain continuous wakefulness (slow process). The data indicate that the temporal organization of vigilance states on both the fast and the slow time scales may arise from a common neurophysiologic mechanism. 相似文献
120.