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71.
Alane Beatriz Vermelho Verônica da Silva Cardoso Eduardo Ricci Junior Elisabete Pereira dos Santos 《Journal of enzyme inhibition and medicinal chemistry》2018,33(1):139-146
Sulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitors targeting the α-class enzyme from the protozoan pathogen Trypanosoma cruzi, responsible of Chagas disease, were recently reported. Although many such derivatives showed low nanomolar activity in vitro, they were inefficient anti-T. cruzi agents in vivo. Here, we show that by formulating such sulfonamides as nanoemulsions in clove (Eugenia caryophyllus) oil, highly efficient anti-protozoan effects are observed against two different strains of T. cruzi. These effects are probably due to an enhanced permeation of the enzyme inhibitor through the nanoemulsion formulation, interfering in this way with the life cycle of the pathogen either by inhibiting pH regulation or carboxylating reactions in which bicarbonate/CO2 are involved. This type of formulation of sulfonamides with T. cruzi CA inhibitory effects may lead to novel therapeutic approaches against this orphan disease. 相似文献
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Domínguez-Escobar J Beltrán Y Bergman B Díez B Ininbergs K Souza V Falcón LI 《FEMS microbiology letters》2011,316(2):90-99
Heterocyst-forming cyanobacteria are important players at both evolutionary and ecological scales, but to date it has been difficult to establish their phylogenetic affiliations. We present data from a phylogenetic and molecular clock analysis of heterocystous cyanobacteria within the family Rivulariaceae, including the genera Calothrix, Rivularia, Gloeotrichia and Tolypothrix. The strains were isolated from distant geographic regions including fresh and brackish water bodies, microbial mats from beach rock, microbialites, pebble beaches, plus PCC strains 7103 and 7504. Phylogenetic inferences (distance, likelihood and Bayesian) suggested the monophyly of genera Calothrix and Rivularia. Molecular clock estimates indicate that Calothrix and Rivularia originated ~1500 million years ago (MYA) ago and species date back to 400-300 MYA while Tolypothrix and Gloeotrichia are younger genera (600-400 MYA). 相似文献
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The hydrodynamic properties of macromolecules and bioparticles, represented by bead models, can be calculated using methods
implemented in the computer routine HYDRO. Recently, a new computer routine, SOLPRO, has been presented for the calculation
of various SOLution PROperties. These include (1) time-dependent electro-optic and spectroscopic properties related to rotational
diffusion, (2) non-dynamic properties like scattering curves, and (3) dimensionless quantities that combine two or more solution
properties in a form which depends on the shape of the macromolecule but not on its size. In the present work we describe
the inclusion of more of those types of properties in a new version of SOLPRO. Particularly, we describe the calculation of
relaxation rates in nuclear magnetic resonance (NMR). For dipolar coupling, given the direction of the dipole the program
calculates values of the spectral density, from which the NMR relaxation times can be obtained. We also consider scattering-related
properties, namely the distribution of distances for the bead model, which is directly related to the angular dependence of
scattered intensity, and the particle's longest distance. We have devised and programmed a procedure to calculate the covolume
of the bead model, related to the second virial coefficient and, in general, to the concentration dependence of solution properties.
Various shape-dependent dimensionless quantities involving the covolume are calculated. In this paper we also discuss some
aspects, namely bead overlapping and hydration, that are not explicitely included in SOLPRO, but should be considered by the
user.
Received: 25 May 1998 / Revised version: 30 July 1998 / Accepted: 30 July 1998 相似文献
78.
Idaira Hueso-Falcón Natalia Girón Pilar Velasco Juan M. Amaro-Luis Angel G. Ravelo Beatriz de las Heras Sonsoles Hortelano Ana Estevez-Braun 《Bioorganic & medicinal chemistry》2010,18(4):1724-1735
Thirty one ent-kaurane derivatives were prepared from kaurenoic acid (1), grandiflorenic acid (16), 15α-acetoxy-kaurenoic acid (26) and 16α-hydroxy-kaurenoic acid (31). They were tested for their ability to inhibit cell viability in the mouse leukemic macrophagic RAW 264.7 cell line. The most effective compounds were 12, 20, 21, and 23. These were selected for further evaluation in other human cancer cell lines such as Hela, HepG2, and HT-29. Similar effects were obtained although RAW 264.7 cells were more sensitive. In addition, these compounds were significantly less cytotoxic in non-transformed cells. The apoptotic potential of the most active compounds was investigated and they were able to induce apoptosis with compound 12 being the best inducer. The caspase-3, -8 and -9 activities were measured. The results obtained showed that compounds 12, 21, and 23 induce apoptosis via the activation of caspase-8, whereas compound 20 induces apoptosis via caspase-9. Immunoblot analysis of the expression of p53, Bax, Bcl-2, Bcl-xl, and IAPs in RAW 264.7 cells was also carried out. When cells were exposed to 5 μM of the different compounds, expression levels of p53 and Bax increased whereas levels of antiapoptotic proteins such as Bc1-2, Bc1-x1, and IAPs decreased. In conclusion, kaurane derivatives (12, 20, 21, and 23) induce apoptosis via both the mitochondrial and membrane death receptor pathways, involving the Bcl-2 family proteins. Taken together these results provide a role of kaurane derivatives as apoptotic inducers in tumor cells. 相似文献
79.
Mitogen-activated protein kinases modulate H(2)O(2)-induced apoptosis in primary rat alveolar epithelial cells 总被引:11,自引:0,他引:11
Carvalho H Evelson P Sigaud S González-Flecha B 《Journal of cellular biochemistry》2004,92(3):502-513
Increasing evidence suggests a role for apoptosis in the maintenance of the alveolar epithelium under normal and pathological conditions. However, the signaling pathways modulating alveolar type II (ATII) cell apoptosis remain poorly defined. Here we investigated the role of MAPKs as modulators of oxidant-mediated ATII cell apoptosis using in vitro models of H(2)O(2)-stress. H(2)O(2), delivered either as a bolus or as a flux, lead to time- and concentration-dependent increases in ATII cells apoptosis. Increased apoptosis in primary rat ATII cells was detected at H(2)O(2) concentrations and production rates in the physiological range (1 microM) and peaked at 100 microM H(2)O(2). Immortalized rat lung epithelial cells (RLE), in contrast, required millimolar concentration of H(2)O(2) for maximal responses. H(2)O(2)-induced apoptosis was preceded by rapid activation of all three classes of mitogen-activated protein kinases (MAPKs): ERK, JNK, and p38. Specific inhibition of JNK using antisense oligonucleotides and ERK and p38 using PD98059 or SB202190, respectively, indicated a pro-apoptotic role for JNK pathway and an anti-apoptotic role for ERK- and p38-initiated signaling events. Our data show that the balance between the activation of JNK, ERK, and p38 is a critical determinant of cell fate, suggesting that pharmacological interventions on the MAPK pathways may be useful in the treatment of oxidant-related lung injury. 相似文献
80.
Alexandre Grangeiro Maria Mercedes Escuder Alex Jones Flores Cassanote Rosa Alencar Souza Artur O. Kalichman Valdiléa Veloso Maria Letícia Rodrigues Ikeda Nêmora Tregnago Barcellos Carlos Brites Unai Tupinanbás Noaldo O. Lucena Carlos Lima da Silva Heloisa Ramos Lacerda Beatriz Grinsztejn Euclides Ayres Castilho 《PloS one》2014,9(5)