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901.
902.
The development of methyl-TROSY approaches and specific (13)C-(1)H labeling of Ile, Leu and Val methyl groups in highly deuterated proteins has made it possible to study high molecular weight proteins, either alone or in complexes, using solution nuclear magnetic resonance (NMR) spectroscopy. Here we present 2-dimensional (2D) and 3-dimensional (3D) NMR experiments designed to achieve complete separation of the methyl resonances of Val and Leu, labeled using the same precursor, α-ketoisovalerate or acetolactate. The 2D experiment can further select the methyl resonances of Val or Leu based on the C(α) or C(β) chemical shift values of Val or Leu, respectively. In the 3D spectrum, the methyl cross peaks of Val and Leu residues have opposite signs; thus, not only can the residue types be easily distinguished, but the methyl pairs from the same residue can also be identified. The feasibility of this approach, implemented in both 2D and 3D experiments, has been demonstrated on an 82 kDa protein, malate synthase G. The methods developed in this study will reduce resonance overlaps and also facilitate structure-guided resonance assignments. 相似文献
903.
Jen-Hsien Weng Shau-Lian Wong Kuan-Ming Lai Rong-Jhih Lin 《Trees - Structure and Function》2012,26(2):343-351
Previously, we found a significant association between photosystem II efficiency (ΦPSII) and photochemical reflectance index
(PRI) measured at predawn among different species at different elevations and throughout several seasons. However, this relationship
has not been evaluated under varied levels of illumination. Here, we used the Taiwan species Pinus
taiwanensis (a conifer distributed at 750–3,000 m a.s.l.), Stranvaesia niitakayamensis (an evergreen tree, 1,700–3,100 m) and two Miscanthus spp. (perennial C4 Gramineae, coastline–3,200 m) to elucidate the ΦPSII–PRI relationship. We studied six levels of photosynthetic photon flux
density (PPFD) (0, 200, 400, 800, 1,200 and 2,000 μmol m−2 s−1) over several growth seasons at high (2,600 m a.s.l.) and low (800 m a.s.l.) elevation sites. In comparing the same species
or genus, ΦPSII and PRI were closely correlated in darkness or under the same level of PPFD, with data obtained from different
seasons and elevations pooled for regression analysis. Because both the intercept and slope of the ΦPSII–PRI equation showed
a negative curvilinear correlation with PPFD, we could fit an empirical regression model, ΦPSII = c + d·ln(PPFD) + e·[ln(PPFD)]2 + f·PRI + g·PRI·ln(PPFD) + h·PRI·[ln(PPFD)]2, for multiple regression analysis. Using this model, we found a close correlation between the estimated and measured ΦPSII
(r
2 = 0.842−0.937, P < 0.001) for all four species examined and for mango (Mangifera indica) measured under both artificial illumination and sunlight (data from Weng et al. 2010). This empirical regression model could simulate both seasonal and diurnal variations of leaf-scale photosynthetic efficiency
at high and low elevations. 相似文献
904.
905.
Canales E Carlson JS Appleby T Fenaux M Lee J Tian Y Tirunagari N Wong M Watkins WJ 《Bioorganic & medicinal chemistry letters》2012,22(13):4288-4292
The use of a tri-substituted acylhydrazine as an isostere of a tertiary amide was explored in a series of HCV NS5B thumb site II inhibitors. Direct replacement generated an analog with similar conformational and physicochemical properties. The series was extended to produce compounds with potent binding affinities and encouraging levels of cellular potency. 相似文献
906.
Chen X Mihalic J Fan P Liang L Lindstrom M Wong S Ye Q Fu Y Jaen J Chen JL Dai K Li L 《Bioorganic & medicinal chemistry letters》2012,22(1):363-366
A series of spiropiperidine carbazoles were synthesized and evaluated as MCHR2 antagonists using a FLIPR assay. The pharmacokinetic properties of selected compounds have also been studied. This effort led to the discovery of potent and specific MCHR2 antagonists. Compound 38 demonstrated good pharmacokinetic properties across rat, beagle dog and rhesus monkey and had a favorable selectivity profile against a number of other receptors. These MCHR2 antagonists are considered appropriate tool compounds for study of the function of MCHR2 in vivo. 相似文献
907.
Leyi Gong Yun-Chou Tan Genevieve Boice Sarah Abbot Kristen McCaleb Pravin Iyer Fengrong Zuo Joseph Dal Porto Brian Wong Sue Jin Alice Chang Patricia Tran Gary Hsieh Linghao Niu Ada Shao Deborah Reuter Christine M. Lukacs R. Ursula Kammlott Andreas Kuglstatter David Goldstein 《Bioorganic & medicinal chemistry letters》2012,22(24):7381-7387
A novel series of highly selective JNK inhibitors based on the 4-quinolone scaffold was designed and synthesized. Structure based drug design was utilized to guide the compound design as well as improvements in the physicochemical properties of the series. Compound (13c) has an IC50 of 62/170 nM for JNK1/2, excellent kinase selectivity and impressive efficacy in a rodent asthma model. 相似文献
908.
909.
Huumonen K Immonen HK Baverstock K Hiltunen M Korkalainen M Lahtinen T Parviainen J Viluksela M Wong G Naarala J Juutilainen J 《Mutation research》2012,743(1-2):36-41
Currently, the cosmetics industry relies on the results of in vitro genotoxicity tests to assess the safety of chemicals. Although the cytokinesis-block micronucleus (CBMN) test for the detection of cells that have divided once is routinely used and currently accepted by regulatory agencies, it has some limitations. Reconstituted human epidermis (RHE) is widely used in safety assessments because its physiological properties resemble those of the skin, and because it allows testing of substances such as hydrophobic compounds. Thus, the micronucleus test is being adapted for application in RHE-reconstructed tissues. Here we investigated whether two different reconstructed epidermis models (EPI/001 from Straticell, and RHE/S/17 from Skinethic) are suitable for application of the micronucleus test. We found that acetone does not modify micronucleus frequency, cell viability, and model structure, compared with non-treated RHE. Treatment of the EPI/001 model with mitomycin C and vinblastine resulted in a dose-dependent increase of micronucleus frequency as well as a decrease of tissue viability and of binucleated cell rate, while no changes of the epidermal structure were observed. The number of binucleated cells obtained with the RHE/S/17 model was too small to permit micronucleus testing. These results indicate that the proliferative rate of the tissue used is a critical parameter in performing the micronucleus test on a 3D model. 相似文献
910.