全文获取类型
收费全文 | 819篇 |
免费 | 74篇 |
出版年
2023年 | 7篇 |
2022年 | 6篇 |
2021年 | 28篇 |
2020年 | 12篇 |
2019年 | 26篇 |
2018年 | 23篇 |
2017年 | 23篇 |
2016年 | 30篇 |
2015年 | 55篇 |
2014年 | 60篇 |
2013年 | 54篇 |
2012年 | 91篇 |
2011年 | 67篇 |
2010年 | 54篇 |
2009年 | 20篇 |
2008年 | 44篇 |
2007年 | 38篇 |
2006年 | 39篇 |
2005年 | 29篇 |
2004年 | 25篇 |
2003年 | 30篇 |
2002年 | 19篇 |
2001年 | 10篇 |
2000年 | 13篇 |
1999年 | 11篇 |
1998年 | 6篇 |
1997年 | 5篇 |
1996年 | 7篇 |
1995年 | 3篇 |
1994年 | 5篇 |
1993年 | 5篇 |
1992年 | 4篇 |
1990年 | 2篇 |
1988年 | 3篇 |
1987年 | 3篇 |
1986年 | 4篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1980年 | 3篇 |
1979年 | 3篇 |
1978年 | 3篇 |
1976年 | 1篇 |
1975年 | 4篇 |
1974年 | 3篇 |
1969年 | 1篇 |
1968年 | 1篇 |
1964年 | 1篇 |
1963年 | 1篇 |
1953年 | 1篇 |
排序方式: 共有893条查询结果,搜索用时 15 毫秒
81.
Lucie Emilie Schmaltz Cédric Juillet Joost Marius Tinbergen Yvonne Ingje Verkuil Joslyn Corstiaan Elbert Wouter Hooijmeijer Theunis Piersma 《Population Ecology》2015,57(4):613-624
The ruff Philomachus pugnax, a lekking shorebird wintering in Africa and breeding across northern Eurasia, declined severely in its western range. Based on a capture-mark-resighting programme (2004–2011) in the westernmost staging area in Friesland (the Netherlands), we investigated changes in apparent annual survival in relation to age and sex to explore potential causes of decline. We also related temporal variation in apparent survival to environmental factors. We used the Capture-Mark-Recapture multievent statistical framework to overcome biases in survival estimates after testing for hidden heterogeneity of detection. This enabled the estimation of the probability to belong to high or low detectability classes. Apparent survival varied between years but was not related to weather patterns along the flyway, or to flood levels in the Sahel. Over time, a decline in apparent survival is suggested. Due to a short data series and flag loss in the last period this cannot be verified. Nevertheless, the patterns in sex-specific detectability and survival lead to new biological insights. Among highly detectable birds, supposedly most reliant on Friesland, males survived better than females ( = 0.74, range 0.51–0.93; = 0.51, range 0.24–0.81). Among low detectable birds, the pattern is reversed ( = 0.64, range 0.37–0.89; = 0.73, range 0.48–0.93). Probably the staging population contains a mixture of sex-specific migration strategies. A loss of staging females could greatly affect the dynamics of the western ruff population. Further unravelling of these population processes requires geographically extended demographic monitoring and the use of tracking devices. 相似文献
82.
Vivek Anand Manivel Azita Sohrabian Marius C Wick Mohammed Mullazehi Lena Douhan H?kansson Johan R?nnelid 《Arthritis research & therapy》2015,17(1)
IntroductionRheumatoid arthritis (RA) patients with autoantibodies against collagen type II (CII) are characterized by acute RA onset with elevated inflammatory measures and early joint erosions as well as increased production of tumor necrosis factor-α (ΤΝF-α) by peripheral blood mononuclear cells (PBMC) stimulated by anti-CII immune complexes (IC) in vitro. Polymorphonuclear granulocytes (PMN) are abundant in RA synovial fluids, where they might interact directly with anti-CII IC in the articular cartilage, but no studies have investigated PMN responses towards anti-CII IC. The aim was to investigate whether PMN react towards anti-CII IC, and to what extent such reactivity might relate to the clinical acute onset RA phenotype associated with elevated levels of anti-CII.MethodsPMN and PBMC isolated from healthy donors were stimulated with IC made with a set of 72 baseline patient sera (24 anti-CII positive, 48 anti-CII negative) chosen from a clinically well-characterized RA cohort with two-year radiological follow-up with Larsen scoring. PMN expression of cluster of differentiation (CD)11b, CD66b, CD16 and CD32 was measured by flow cytometry, whereas PMN production of myeloperoxidase (MPO) and interleukin (IL)-17, and PBMC production of ΤΝF-α was measured with enzyme linked immunosorbent assay.ResultsPMN expression of CD11b, CD66b and MPO, and PBMC production of ΤΝF-α were upregulated whereas PMN expression of CD16 and CD32 were downregulated by anti-CII IC. CD16, CD66b, and MPO production correlated to serum anti-CII levels (Spearman’s ρ = 0.315, 0.675 and 0.253, respectively). CD16 was associated with early joint erosions (P = 0.024, 0.034, 0.046 at baseline, one and two years) and CD66b was associated with changes in joint erosions (P = 0.017 and 0.016, at one and two years compared to baseline, respectively). CD66b was associated with baseline C-reactive protein and PBMC production of ΤΝF-α was associated with baseline erythrocyte sedimentation rate, in accordance with our earlier findings. No clinical associations were observed for MPO or IL-17.ConclusionPMN responses against anti-CII IC are more closely associated with early joint erosions than are PBMC cytokine responses. PMN reactivity against anti-CII IC may contribute to joint destruction in newly diagnosed RA patients with high levels of anti-CII. 相似文献
83.
Fawzi NL Fleissner MR Anthis NJ Kálai T Hideg K Hubbell WL Clore GM 《Journal of biomolecular NMR》2011,51(1-2):105-114
The measurement of (1)H transverse paramagnetic relaxation enhancement (PRE) has been used in biomolecular systems to determine long-range distance restraints and to visualize sparsely-populated transient states. The intrinsic flexibility of most nitroxide and metal-chelating paramagnetic spin-labels, however, complicates the quantitative interpretation of PREs due to delocalization of the paramagnetic center. Here, we present a novel, disulfide-linked nitroxide spin label, R1p, as an alternative to these flexible labels for PRE studies. When introduced at solvent-exposed α-helical positions in two model proteins, calmodulin (CaM) and T4 lysozyme (T4L), EPR measurements show that the R1p side chain exhibits dramatically reduced internal motion compared to the commonly used R1 spin label (generated by reacting cysteine with the spin labeling compound often referred to as MTSL). Further, only a single nitroxide position is necessary to account for the PREs arising from CaM S17R1p, while an ensemble comprising multiple conformations is necessary for those observed for CaM S17R1. Together, these observations suggest that the nitroxide adopts a single, fixed position when R1p is placed at solvent-exposed α-helical positions, greatly simplifying the interpretation of PRE data by removing the need to account for the intrinsic flexibility of the spin label. 相似文献
84.
Mayer KF Martis M Hedley PE Simková H Liu H Morris JA Steuernagel B Taudien S Roessner S Gundlach H Kubaláková M Suchánková P Murat F Felder M Nussbaumer T Graner A Salse J Endo T Sakai H Tanaka T Itoh T Sato K Platzer M Matsumoto T Scholz U Dolezel J Waugh R Stein N 《The Plant cell》2011,23(4):1249-1263
We used a novel approach that incorporated chromosome sorting, next-generation sequencing, array hybridization, and systematic exploitation of conserved synteny with model grasses to assign ~86% of the estimated ~32,000 barley (Hordeum vulgare) genes to individual chromosome arms. Using a series of bioinformatically constructed genome zippers that integrate gene indices of rice (Oryza sativa), sorghum (Sorghum bicolor), and Brachypodium distachyon in a conserved synteny model, we were able to assemble 21,766 barley genes in a putative linear order. We show that the barley (H) genome displays a mosaic of structural similarity to hexaploid bread wheat (Triticum aestivum) A, B, and D subgenomes and that orthologous genes in different grasses exhibit signatures of positive selection in different lineages. We present an ordered, information-rich scaffold of the barley genome that provides a valuable and robust framework for the development of novel strategies in cereal breeding. 相似文献
85.
86.
Van Campenhout CA Eitelhuber A Gloeckner CJ Giallonardo P Gegg M Oller H Grant SG Krappmann D Ueffing M Lickert H 《Developmental cell》2011,21(3):479-491
The Drosophila Discs large (Dlg) scaffolding protein acts as a tumor suppressor regulating basolateral epithelial polarity and proliferation. In mammals, four Dlg homologs have been identified; however, their functions in cell polarity remain poorly understood. Here, we demonstrate that the X-linked mental retardation gene product Dlg3 contributes to apical-basal polarity and epithelial junction formation in mouse organizer tissues, as well as to planar cell polarity in the inner ear. We purified complexes associated with Dlg3 in polarized epithelial cells, including proteins regulating directed trafficking and tight junction formation. Remarkably, of the four Dlg family members, Dlg3 exerts a distinct function by recruiting the ubiquitin ligases Nedd4 and Nedd4-2 through its PPxY motifs. We found that these interactions are required for Dlg3 monoubiquitination, apical membrane recruitment, and tight junction consolidation. Our findings reveal an unexpected evolutionary diversification of the vertebrate Dlg family in basolateral epithelium formation. 相似文献
87.
Caşcaval D Galaction AI Turnea M 《Journal of industrial microbiology & biotechnology》2011,38(9):1449-1466
Study of the distribution of the oxygen mass transfer coefficient, k
l
a, for a stirred bioreactor and simulated (pseudoplastic solutions of carboxymethylcellulose sodium salt) bacterial (P. shermanii), yeast (S. cerevisiae), and fungal (P. chrysogenum free mycelia) broths indicated significant variation of transfer rate with bioreactor height. The magnitude of the influence
of the considered factors differed from one region to another. As a consequence of cell adsorption to bubble surface, the
results indicated the impossibility of achieving a uniform oxygen transfer rate throughout the whole bulk of the microbial
broth, even when respecting the conditions for uniform mixing. Owing to the different affinity of biomass for bubble surface,
the positive influence of power input on k
l
a is more important for fungal broths, while increasing aeration is favorable only for simulated, bacterial and yeast broths.
The influence of the considered factors on k
l
a were included in mathematical correlations established based on experimental data. For all considered positions, the proposed
equations for real broths have the general expression
kl a = aCXb ( \fracPa V )g vSd , k_{\rm l} a = \alpha C_{\rm X}^{\beta } \left( {{\frac{{P_{\rm a} }}{V}}} \right)^{\gamma } v_{\rm S}^{\delta } , exhibiting good agreement with experimental results (with maximum deviations of ±10.7% for simulated broths, ±8.4% for P. shermanii, ±9.3% for S. cerevisiae, and ±6.6% for P. chrysogenum). 相似文献
88.
Grozav AG Willard BB Kozuki T Chikamori K Micluta MA Petrescu AJ Kinter M Ganapathi R Ganapathi MK 《Proteomics》2011,11(5):829-842
Topoisomerase (topo) II catalyzes topological changes in DNA. Although both human isozymes, topo IIα and β are phosphorylated, site‐specific phosphorylation of topo IIβ is poorly characterized. Using LC‐MS/MS analysis of topo IIβ, cleaved with trypsin, Arg C or cyanogen bromide (CNBr) plus trypsin, we detected four +80‐Da modified sites: tyr656, ser1395, thr1426 and ser1545. Phosphorylation at ser1395, thr1426 and ser1545 was established based on neutral loss of H3PO4 (?98 Da) in the CID spectra and on differences in 2‐D‐phosphopeptide maps of 32P‐labeled wild‐type (WT) and S1395A or T1426A/S1545A mutant topo IIβ. However, phosphorylation at tyr656 could not be verified by 2‐D‐phosphopeptide mapping of 32P‐labeled WT and Y656F mutant protein or by Western blotting with phosphotyrosine‐specific antibodies. Since the +80‐Da modification on tyr656 was observed exclusively during cleavage with CNBr and trypsin, this modification likely represented bromination, which occurred during CNBr cleavage. Re‐evaluation of the CID spectra identified +78/+80‐Da fragment ions in CID spectra of two peptides containing tyr656 and tyr711, confirming bromination. Interestingly, mutation of only tyr656, but not ser1395, thr1326 or ser1545, decreased topo IIβ activity, suggesting a functional role for tyr656. These results, while identifying an important tyrosine in topo IIβ, underscore the importance of careful interpretation of modifications having the same nominal mass. 相似文献
89.
90.
Frans B Waldorff Volkert Siersma Ruth Ertmann Marius Brostrøm Kousgaard Anette Sonne Nielsen Peter Felding Niels Mosbæk Else Hjortsø Susanne Reventlow 《Implementation science : IS》2011,6(1):1-7