全文获取类型
收费全文 | 984篇 |
免费 | 105篇 |
国内免费 | 2篇 |
出版年
2022年 | 8篇 |
2021年 | 12篇 |
2020年 | 7篇 |
2019年 | 8篇 |
2018年 | 22篇 |
2017年 | 21篇 |
2016年 | 31篇 |
2015年 | 43篇 |
2014年 | 45篇 |
2013年 | 51篇 |
2012年 | 76篇 |
2011年 | 79篇 |
2010年 | 43篇 |
2009年 | 52篇 |
2008年 | 57篇 |
2007年 | 78篇 |
2006年 | 78篇 |
2005年 | 69篇 |
2004年 | 68篇 |
2003年 | 42篇 |
2002年 | 70篇 |
2001年 | 9篇 |
2000年 | 13篇 |
1999年 | 6篇 |
1998年 | 12篇 |
1997年 | 5篇 |
1996年 | 15篇 |
1995年 | 7篇 |
1994年 | 8篇 |
1993年 | 5篇 |
1992年 | 4篇 |
1991年 | 4篇 |
1990年 | 2篇 |
1989年 | 3篇 |
1986年 | 2篇 |
1985年 | 4篇 |
1984年 | 2篇 |
1983年 | 3篇 |
1981年 | 2篇 |
1980年 | 4篇 |
1978年 | 3篇 |
1971年 | 1篇 |
1965年 | 1篇 |
1949年 | 1篇 |
1943年 | 1篇 |
1932年 | 1篇 |
1930年 | 1篇 |
1929年 | 2篇 |
1928年 | 1篇 |
1924年 | 1篇 |
排序方式: 共有1091条查询结果,搜索用时 671 毫秒
191.
Andrey E. Shchekotikhin Valeria A. Glazunova Lyubov G. Dezhenkova Yuri N. Luzikov Yuri B. Sinkevich Leonid V. Kovalenko Vladimir N. Buyanov Jan Balzarini Fong-Chun Huang Jing-Jer Lin Hsu-Shan Huang Alexander A. Shtil Maria N. Preobrazhenskaya 《Bioorganic & medicinal chemistry》2009,17(5):1861-1869
We developed the synthesis of a series of thiophene-fused tetracyclic analogues of the antitumor drug ametantrone. The reactions included nucleophilic substitution of methoxy groups in 4,11-dimethoxyanthra[2,3-b]thiophene-5,10-diones with ethylenediamines, producing the derivatives of 4,11-diaminoanthra[2,3-b]thiophene-5,10-dione in good yields. Several compounds showed marked antiproliferative potency against doxorubicin-selected, P-glycoprotein-expressing tumor cells and p53?/? cells. The cytotoxicity of some novel compounds for P-glycoprotein-positive cells is highly dependent on N-substituent at the terminal amino group of ethylenediamine moiety. The cytotoxic potency of selected compounds correlated with their ability to attenuate the functions of topoisomerase I and telomerase, strongly suggesting that these enzymes are the major targets of antitumor activity of anthra[2,3-b]thiophene-5,10-dione derivatives. 相似文献
192.
193.
We studied the common kinematic features of the coxa and trochanter in cursorial and raptorial legs, which are the short size of the podomers, predominantly monoaxial joints, and the approximate orthogonality of adjacent joint axes. The chain coxa-trochanter with its short elements and serial orthogonality of joint axes resembles the gimbals which combine versatility and tolerance to external perturbations. The geometry of legs was studied in 23 insect species of 12 orders. Insects with monoaxial joints were selected. The joint between the trochanter and the femur (TFJ) is defined either by two vestigial condyles or by a straight anterior hinge. Direction of the joint axes in the two basal podomers was assessed by 3D measurements or by goniometry in two planes. Length of the coxa is <15% (mostly <8%) of the total length of the cursorial leg, that of the trochanter <10%. Angles between the proximal and distal joint axes in the middle coxa range from 124 to 84 degrees (mean 97+/-14 degrees ), in the trochanter (in all legs studied) from 125 to 72 degrees (mean 90+/-13 degrees ). Vectors of the distal axis in the coxa are concentrated about the normal to the plane defined by the proximal axis and the midpoint between the distal condyles. These vectors in the trochanter lie at various angles to the normal; angles are correlated with the direction of the TFJ relative to the femur. Range of reduction about the TFJ is over 60 degrees in the foreleg of Ranatra linearis, Mantispa lobata and the hind leg in Carabus coriaceus (confirming observations of previous authors), 40-60 degrees in the foreleg of Vespa crabro and in the middle one in Ammophila campestris, 10-30 degrees in other studied specimens. The special role of the trochanter in autotomy and in active propulsion in some insect groups is discussed. The majority of insects possess small trochanters and slightly movable TFJs with the joint axis laying in the femur-tibia plane. We pose the hypothesis that the TFJ damps external forces, the vectors of which lie off the femur-tibia plane, the reductor muscle acting as a spring. Thus the TFJ contributes to dynamic stability of legged locomotion. 相似文献
194.
Wolfgang Resch Leonid Zaslavsky Boris Kiryutin Michael Rozanov Yiming Bao Tatiana A Tatusova 《BMC microbiology》2009,9(1):65-7
Background
There is an increasing number of complete and incomplete virus genome sequences available in public databases. This large body of sequence data harbors information about epidemiology, phylogeny, and virulence. Several specialized databases, such as the NCBI Influenza Virus Resource or the Los Alamos HIV database, offer sophisticated query interfaces along with integrated exploratory data analysis tools for individual virus species to facilitate extracting this information. Thus far, there has not been a comprehensive database for dengue virus, a significant public health threat. 相似文献195.
Nicola Saino Diego Rubolini Esa Lehikoinen Leonid V. Sokolov Andrea Bonisoli-Alquati Roberto Ambrosini Giuseppe Boncoraglio Anders P. M?ller 《Biology letters》2009,5(4):539-541
Phenological responses to climate change vary among taxa and across trophic levels. This can lead to a mismatch between the life cycles of ecologically interrelated populations (e.g. predators and prey), with negative consequences for population dynamics of some of the interacting species. Here we provide, to our knowledge, the first evidence that climate change might disrupt the association between the life cycles of the common cuckoo (Cuculus canorus), a migratory brood parasitic bird, and its hosts. We investigated changes in timing of spring arrival of the cuckoo and its hosts throughout Europe over six decades, and found that short-distance, but not long-distance, migratory hosts have advanced their arrival more than the cuckoo. Hence, cuckoos may keep track of phenological changes of long-distance, but not short-distance migrant hosts, with potential consequences for breeding of both cuckoo and hosts. The mismatch to some of the important hosts may contribute to the decline of cuckoo populations and explain some of the observed local changes in parasitism rates of migratory hosts. 相似文献
196.
197.
Olga O. Nerusheva Natalia V. Dorogova Leonid V. Omelyanchuk 《Central European Journal of Biology》2009,4(4):452-460
Localization of a set of chimeric GFP proteins in D. melanogaster spermatogenesis has been studied. In the collection used, the proteins with detectable germ-line expression frequently occur
to be involved in mRNA maturation. According to the cellular localization, proteins fall into three groups, namely, the protein
Rtc1, involved in splicing, displays an exclusively nuclear localization; the proteins Squid (splicing and mRNA transport),
Pabp2 (polyadenylation), and Hrb98DE (splicing and mRNA transport) change their localization during germ-line development;
and the protein Imp (mRNA localization) is located exclusively in the cytoplasm. The distribution of Rtc1, Squid and Hrb98DE
in the spermatocyte nuclei is morphologically similar to the distribution of splicing bodies, the so-called splicing factor
compartments. The proteins Imp and Hrb98DE at the stage of elongation are localized to a specialized structure in the caudal
region of cyst; this region corresponds to the site of the highest synthetic activity in the cyst cells at this developmental
stage. 相似文献
198.
Recombination rate and linkage disequilibrium, the latter a function of population genomic processes, are the critical parameters for mapping by linkage and association, and their patterns in Caenorhabditis elegans are poorly understood. We performed high-density SNP genotyping on a large panel of recombinant inbred advanced intercross lines (RIAILs) of C. elegans to characterize the landscape of recombination and, on a panel of wild strains, to characterize population genomic patterns. We confirmed that C. elegans autosomes exhibit discrete domains of nearly constant recombination rate, and we show, for the first time, that the pattern holds for the X chromosome as well. The terminal domains of each chromosome, spanning about 7% of the genome, exhibit effectively no recombination. The RIAILs exhibit a 5.3-fold expansion of the genetic map. With median marker spacing of 61 kb, they are a powerful resource for mapping quantitative trait loci in C. elegans. Among 125 wild isolates, we identified only 41 distinct haplotypes. The patterns of genotypic similarity suggest that some presumed wild strains are laboratory contaminants. The Hawaiian strain, CB4856, exhibits genetic isolation from the remainder of the global population, whose members exhibit ample evidence of intercrossing and recombining. The population effective recombination rate, estimated from the pattern of linkage disequilibrium, is correlated with the estimated meiotic recombination rate, but its magnitude implies that the effective rate of outcrossing is extremely low, corroborating reports of selection against recombinant genotypes. Despite the low population, effective recombination rate and extensive linkage disequilibrium among chromosomes, which are techniques that account for background levels of genomic similarity, permit association mapping in wild C. elegans strains. 相似文献
199.
Hantgan RR Stahle MC Connor JH Horita DA Rocco M McLane MA Yakovlev S Medved L 《Protein science : a publication of the Protein Society》2006,15(8):1893-1906
This study tested the hypothesis that high-affinity binding of macromolecular ligands to the alphaIIbbeta3 integrin is tightly coupled to binding-site remodeling, an induced-fit process that shifts a conformational equilibrium from a resting toward an open receptor. Interactions between alphaIIbbeta3 and two model ligands-echistatin, a 6-kDa recombinant protein with an RGD integrin-targeting sequence, and fibrinogen's gamma-module, a 30-kDa recombinant protein with a KQAGDV integrin binding site-were measured by sedimentation velocity, fluorescence anisotropy, and a solid-phase binding assay, and modeled by molecular graphics. Studying echistatin variants (R24A, R24K, D26A, D26E, D27W, D27F), we found that electrostatic contacts with charged residues at the alphaIIb/beta3 interface, rather than nonpolar contacts, perturb the conformation of the resting integrin. Aspartate 26, which interacts with the nearby MIDAS cation, was essential for binding, as D26A and D26E were inactive. In contrast, R24K was fully and R24A partly active, indicating that the positively charged arginine 24 contributes to, but is not required for, integrin recognition. Moreover, we demonstrated that priming--i.e., ectodomain conformational changes and oligomerization induced by incubation at 35 degrees C with the ligand-mimetic peptide cHarGD--promotes complex formation with fibrinogen's gamma-module. We also observed that the gamma-module's flexible carboxy terminus was not required for alphaIIbbeta3 integrin binding. Our studies differentiate priming ligands, which bind to the resting receptor and perturb its conformation, from regulated ligands, where binding-site remodeling must first occur. Echistatin's binding energy is sufficient to rearrange the subunit interface, but regulated ligands like fibrinogen must rely on priming to overcome conformational barriers. 相似文献
200.
Krizanauskiene A Hellgren O Kosarev V Sokolov L Bensch S Valkiunas G 《The Journal of parasitology》2006,92(6):1319-1324
A parasite's shift to a new host may have serious evolutionary consequences, since host switching usually is associated with a change in virulence and may lead to the evolution of emerging diseases. This phenomenon remains insufficiently studied in wildlife. Here, we combine microscopic examination of blood films and PCR-based methods to investigate the natural host specificity of Haemoproteus and Plasmodium spp. in birds of 4 families of the Passeriformes within a small geographic area. The material was collected on the Curonian Spit in the Baltic Sea between May and July in 2003-2004. A nested-PCR protocol was used for amplifying and sequencing a fragment of 480 nucleotides of the cytochrome b gene of the mtDNA of these parasites. Blood samples from 282 birds, which were positive both by microscopic examination of blood films and mtDNA amplification, were used in this study. We found that Haemoproteus majoris (lineages hPARUS1, hCCF5, hWW2, and hPHSIB1), Haemoproteus sp. (hWW1), Plasmodium (Haemamoeba) sp. (pSGS1), and Plasmodium (Haemamoeba) sp. (pGRW11) are capable of infecting birds belonging to different families of passeriform birds. Some species of Haemoproteus are less specific than have been traditionally believed. Haemoproteus majoris appears to have a genetic predisposition to have a broad host range. The level of host specificity varies markedly among different species of hemosporidian parasites of birds. The natural host range is thus not a reliable taxonomic character in the systematics of these parasites in the form in which it is still accepted in some recent taxonomic studies. 相似文献