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941.
Bolten KE Marsh AE Reed SM Dubey JP Toribio RE Saville WJ 《Experimental parasitology》2008,120(1):108-112
Sarcocystis neurona causes protozoal myeloencephalitis and has the ability to infect a wide host range in contrast to other Sarcocystis species. In the current study, five S. neurona isolates from a variety of sources, three Sarcocystis falcatula, one Sarcocystis dasypi/S. neurona-like isolate, and one Besnoitia darlingi isolate were used to compare the enolase 2 gene segment containing the domain I region to previously sequenced enolase genes from Neospora caninum, Neospora hughesi, Toxoplasma gondii, Plasmodium falciparum, and Trypanosoma cruzi; enolase 2 segment containing domain I region is highly conserved amongst these parasites of veterinary and medical importance. Immunohistochemistry results indicates reactivity of T. gondii enolase 1 and 2 antibodies to S. neurona merozoites and metrocytes, but no reactivity of anti-enolase 1 to the S. neurona bradyzoite stage despite reactivity to T. gondii bradyzoites, suggesting expression differences between organisms. 相似文献
942.
Shen W Fakhoury S Donner G Henry K Lee J Zhang H Cohen J Warner R Saeed B Cherian S Tahir S Kovar P Bauch J Ng SC Marsh K Sham H Rosenberg S 《Bioorganic & medicinal chemistry letters》1999,9(5):703-708
Synthesis and biological evaluation of heteroarenes as reduced cysteine replacements are described. Of the heteroaryl groups examined with respect to FT inhibitor FTI-276 (1), pyridyl was the replacement found to be most effective. Substitutions at C4 of the pyridyl moiety did not affect the in vitro activity. Compound 9a was found to have moderate in vivo bioavailability. 相似文献
943.
Vicki Xafis G. Owen Schaefer Markus K. Labude Yujia Zhu Soren Holm Roger Sik-Yin Foo Poh San Lai Ruth Chadwick 《PLoS genetics》2021,17(9)
Much has been written about gene modifying technologies (GMTs), with a particularly strong focus on human germline genome editing (HGGE) sparked by its unprecedented clinical research application in 2018, shocking the scientific community. This paper applies political, ethical, and social lenses to aspects of HGGE to uncover previously underexplored considerations that are important to reflect on in global discussions. By exploring 4 areas—(1) just distribution of HGGE benefits through a realist lens; (2) HGGE through a national interest lens; (3) “broad societal consensus” through a structural injustice lens; and (4) HGGE through a scientific trustworthiness lens—a broader perspective is offered, which ultimately aims to enrich further debates and inform well-considered solutions for developments in this field. The application of these lenses also brings to light the fact that all discussions about scientific developments involve a conscious or unconscious application of a lens that shapes the direction of our thinking. 相似文献
944.
Grazing by dugongs and cropping by green turtles have the capacity to alter the subsequent nutritional quality of seagrass
regrowth. We examined the effects of simulated light and intensive grazing by dugongs and cropping by turtles on eight nutritionally
relevant measures of seagrass chemical composition over two regrowth periods (short-term, 1–4 months; long-term, 11–13 months)
at two seagrass communities (a mixed species community with Zostera capricorni, Halophila ovalis, Halodule uninervis, Cymodocea rotundata and C. serrulate; and a monospecific bed of Halodule uninervis) in tropical Queensland, Australia. The concentrations of organic matter, total nitrogen, total water-soluble carbohydrates,
total starch, neutral detergent fiber, acid detergent fiber, acid lignin, as well as the in vitro dry matter digestibility
(IVDMD) were measured in the leaves and below-ground parts of each species using near-infrared reflectance spectroscopy (NIRS).
Regrowth of preferred species such as H. ovalis and H. uninervis from simulated intensive dugong grazing after a year exhibited increased (by 35 and 25%, respectively, relative to controls)
whole-plant N concentrations. Similarly, regrowth of H. ovalis from simulated turtle cropping showed an increase in the leaf N concentration of 30% after a year. However, these gains are
tempered by reductions in starch concentrations and increases in fiber. In the short-term, the N concentrations increased
while the fiber concentrations decreased. These data provide experimental support for a grazing optimization view of herbivory
in the tropical seagrass system, but with feedback in a different manner. Furthermore, we suggest that in areas where grazing
is the only major source of natural disturbance, it is likely that there are potential ecosystem level effects if and when
numbers of dugongs and turtles are reduced. 相似文献
945.
Marsh L 《Journal of molecular evolution》2006,62(5):575-587
The globin family of proteins has a characteristic structural pattern of helix interactions that nonetheless exhibits some
variation. A simplified model for globin structural evolution was developed in which protein shape evolved by random change
of contacts between helices. A conserved globin domain of 15 bacterial proteins representing four structural families was
studied. Using a parsimony approach ancestral structural states could be reconstructed. The distribution of number of contact
changes per site for a fixed topology tree fit a gamma distribution. Homoplasy was high, with multiple changes per site and
no support for an invariant class of residue-residue contacts. Contacts changed more slowly than sequence. A phylogenetic
reconstruction using a distance measure based on the proportion of shared contacts was generally consistent with a sequence-based
phylogeny but not highly resolved. Contact pattern convergence between members of different globin family proteins could not
be detected. Simulation studies indicated the convergence test was sensitive enough to have detected convergence involving
only 10% of the contacts, suggesting a limit on the extent of selection for a specific contact pattern. Contact site methods
may provide additional approaches to study the relationship between protein structure and sequence evolution.
[Reviewing Editior: Dr. Lauren Ancel Meyers] 相似文献
946.
947.
Pichia pastoris fermentation optimization: energy state and testing a growth-associated model 总被引:1,自引:0,他引:1
Plantz BA Sinha J Villarete L Nickerson KW Schlegel VL 《Applied microbiology and biotechnology》2006,72(2):297-305
A growth-associated model was applied to the production of recombinant ovine interferon-τ (rOvIFN-τ) with Pichia pastoris for the purpose of manufacturing preclinical and clinical active material. This model predicts that product yields will be the greatest when the specific growth of the culture is maintained at a steady and optimal rate. However, rOvIFN-τ yields did not meet the expected linear model but most closely corresponded to a polynomial relationship. After transitioning from glycerol to methanol, product accumulated for 31–45 h, and then the yield decreased. This production shift, which has been termed decoupling, was clearly related to time on methanol and not culture density. It was determined that a correlation exists between the decoupling point and a drop in energy state of the cell when expressing β-galactosidase. By assigning decoupling as a constraint that limits productivity and by reformulating the growth medium, the time prior to decoupling increased to 46.8±2.4 h, product yield improved for rOvIFN-τ from 203 to 337 mg l−1, and the coefficient of variation for yield decreased from 67.9 to 23.3%. A robust and stable fermentation process was realized, resulting in a 210% improvement in total yield from 557±357 to 1,172±388 mg. 相似文献
948.
Hill J Murray L Leidecker V Sharp H 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》2008,363(1503):2529-2541
This paper considers how environmental threat may contribute to the child's use of avoidant strategies to regulate negative emotions, and how this may interact with high emotional reactivity to create vulnerability to conduct disorder symptoms. We report a study based on the hypothesis that interpreting others' behaviours in terms of their motives and emotions-using the intentional stance-promotes effective social action, but may lead to fear in threatful situations, and that inhibiting the intentional stance may reduce fear but promote conduct disorder symptoms. We assessed 5-year-olds' use of the intentional stance with an intentionality scale, contrasting high and low threat doll play scenarios. In a sample of 47 children of mothers with post-natal depression (PND) and 35 controls, children rated as securely attached with their mothers at the age of 18 months were better able to preserve the intentional stance than insecure children in high threat scenarios, but not in low threat scenarios. Girls had higher intentionality scores than boys across all scenarios. Only intentionality in the high threat scenario was associated with teacher-rated conduct disorder symptoms, and only in the children of women with PND. Intentionality mediated the associations between attachment security and gender and conduct disorder symptoms in the PND group. 相似文献
949.
Drizin I Gregg RJ Scanio MJ Shi L Gross MF Atkinson RN Thomas JB Johnson MS Carroll WA Marron BE Chapman ML Liu D Krambis MJ Shieh CC Zhang X Hernandez G Gauvin DM Mikusa JP Zhu CZ Joshi S Honore P Marsh KC Roeloffs R Werness S Krafte DS Jarvis MF Faltynek CR Kort ME 《Bioorganic & medicinal chemistry》2008,16(12):6379-6386
The synthesis and pharmacological characterization of a novel furan-based class of voltage-gated sodium channel blockers is reported. Compounds were evaluated for their ability to block the tetrodotoxin-resistant sodium channel Na(v)1.8 (PN3) as well as the Na(v)1.2 and Na(v)1.5 subtypes. Benchmark compounds from this series possessed enhanced potency, oral bioavailability, and robust efficacy in a rodent model of neuropathic pain, together with improved CNS and cardiovascular safety profiles compared to the clinically used sodium channel blockers mexiletine and lamotrigine. 相似文献
950.
The mechanisms contributing to worsening of asthma during pregnancy have not been well characterized. Both asthma and pregnancy are conditions associated with a skewing of the immune response from T helper (Th) 1 toward a Th2 response. We hypothesise that worsening of asthma during pregnancy may be due to an enhanced production of circulating proinflammatory cytokines and chemokines and this may be modified by the use of inhaled glucocorticoid treatment. Peripheral blood was collected from asthmatic (n = 35) and control non-asthmatic patients (n = 13) in the third trimester (30–37 weeks) of pregnancy. Fetal blood was collected from the umbilical vein of the placenta after delivery from normal (n = 24) and pregnancies complicated by asthma (n = 24). Plasma samples were assayed for IL-6, -8, eotaxin and RANTES using conventional ELISA. In addition, a range of Th1 and Th2 cytokines measured using Luminex system. There were no significant differences in the levels of maternal IL-6, IL-8, eotaxin and RANTES between asthmatics and nonasthmatics. The results of this study suggest that the presence of asthma does not result in an enhanced circulation of Th2 related cytokines and chemokines during the third trimester of pregnancy. Furthermore peripheral blood cytokine concentrations appear unaffected by inhaled glucocorticoid treatment. Cord plasma eotaxin concentrations were increased in pregnancies complicated by asthma, compared with control. This is the first study to show increased eotaxin production in the feto-placental unit of asthmatic pregnancies and may be one mechanism by which allergy susceptibility is increased in the offspring of asthmatic women. 相似文献