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111.
James Kempson Junqing Guo Jagabandhu Das Robert V. Moquin Steven H. Spergel Scott H. Watterson Charles M. Langevine Alaric J. Dyckman Mark Pattoli James R. Burke XiaoXia Yang Kathleen M. Gillooly Kim W. McIntyre Laishun Chen John H. Dodd Murray McKinnon Joel C. Barrish William J. Pitts 《Bioorganic & medicinal chemistry letters》2009,19(10):2646-2649
A new series of tricyclic-based inhibitors of IKK have been derived from an earlier lead compound. The synthesis and structure–activity relationships (SAR) are described. Compound 4k inhibited TNF production in rats stimulated with LPS. 相似文献
112.
We used live-trapping and foraging to test for the effect of habitat selection and diet on structuring a community of six small mammals and one bird within the Soutpansberg, South Africa. We established grids that straddled adjacent habitats: woodland, rocky hillside, and grassland. Trapping and foraging were used to estimate abundance, habitat use, and species-specific foraging costs. The species with the highest abundance and foraging activity in a habitat, activity time, or food was considered the most efficient and presumed to have a competitive advantage. All species exhibited distinct patterns of spatial and temporal habitat preference which provided the main mechanism of coexistence, followed by diet selection. The study species were organized into three assemblages (α diversity): grassland, Rhabdomys pumilio, Dendromus melanotis, and Mus minutoides.; woodland, Aethomys ineptus and Micaelamys namaquensis; and rock-dwelling, M. namaquensis and Elephantulus myurus. Francolinus natalensis foraged in open rocky areas and under wooded islands within the grassland. Species organization across the habitats suggested that feeding opportunities are available within all habitats; however, distinct habitat preferences resulted from differing foraging aptitudes and efficiencies of the competing species. At Lajuma, species distribution and coexistence are promoted through distinct habitat preferences that were shaped by competition and species-specific foraging costs. The combination of trapping and foraging provided a mechanistic approach that integrates behavior into community ecology by ‘asking’ the animal to reveal its perspective of the environment. Using spatial and temporal foraging decisions—as behavioral indicators—enables us to guide our understanding for across-taxa species coexistence. 相似文献
113.
SAM domain-based protein oligomerization observed by live-cell fluorescence fluctuation spectroscopy
Sterile-alpha-motif (SAM) domains are common protein interaction motifs observed in organisms as diverse as yeast and human. They play a role in protein homo- and hetero-interactions in processes ranging from signal transduction to RNA binding. In addition, mutations in SAM domain and SAM-mediated oligomers have been linked to several diseases. To date, the observation of heterogeneous SAM-mediated oligomers in vivo has been elusive, which represents a common challenge in dissecting cellular biochemistry in live-cell systems. In this study, we report the oligomerization and binding stoichiometry of high-order, multi-component complexes of (SAM) domain proteins Ste11 and Ste50 in live yeast cells using fluorescence fluctuation methods. Fluorescence cross-correlation spectroscopy (FCCS) and 1-dimensional photon counting histogram (1dPCH) confirm the SAM-mediated interaction and oligomerization of Ste11 and Ste50. Two-dimensional PCH (2dPCH), with endogenously expressed proteins tagged with GFP or mCherry, uniquely indicates that Ste11 and Ste50 form a heterogeneous complex in the yeast cytosol comprised of a dimer of Ste11 and a monomer of Ste50. In addition, Ste50 also exists as a high order oligomer that does not interact with Ste11, and the size of this oligomer decreases in response to signals that activate the MAP kinase cascade. Surprisingly, a SAM domain mutant of Ste50 disrupted not only the Ste50 oligomers but also Ste11 dimerization. These results establish an in vivo model of Ste50 and Ste11 homo- and hetero-oligomerization and highlight the usefulness of 2dPCH for quantitative dissection of complex molecular interactions in genetic model organisms such as yeast. 相似文献
114.
P. C. Vincent G. Borner A. D. Chanana E. P. Cronkite M. L. Greenberg D. D. Joel L. M. Schiffer P. A. Stryckmans 《Cell proliferation》1969,2(3):235-247
Some of the time parameters of the cell cycle in bovine thoracic duct lymphocytes have been estimated by analysing labeled mitoses curves, and by double labeling. The two methods gave similar estimates of Ts. Thus, Ts measured directly from labeled mitoses curves varied from 4 to 6 hr, while the estimates from double labeling were 4.8 and 4.5 hr. T G measured directly from labeled mitoses curves was 5 hr, and estimates of TG from the values of Ts ranged from 6.3 to 7.7 hr. The present data confirm the short generative cycle of large thoracic duct lymphocytes. Extracorporeal irradiation of the lymph (ECIL) had no detectable effect on the cell cycle or the fractional production rate of the lymphocytes. However, the calculated absolute production was reduced following ECIL, due to a decrease in the absolute number of cells present. The grain count over mitoses after ECIL was approximately one-half that found before ECIL. 相似文献
115.
Wang CI Guncar G Forwood JK Teh T Catanzariti AM Lawrence GJ Loughlin FE Mackay JP Schirra HJ Anderson PA Ellis JG Dodds PN Kobe B 《The Plant cell》2007,19(9):2898-2912
The gene-for-gene mechanism of plant disease resistance involves direct or indirect recognition of pathogen avirulence (Avr) proteins by plant resistance (R) proteins. Flax rust (Melampsora lini) AvrL567 avirulence proteins and the corresponding flax (Linum usitatissimum) L5, L6, and L7 resistance proteins interact directly. We determined the three-dimensional structures of two members of the AvrL567 family, AvrL567-A and AvrL567-D, at 1.4- and 2.3-A resolution, respectively. The structures of both proteins are very similar and reveal a beta-sandwich fold with no close known structural homologs. The polymorphic residues in the AvrL567 family map to the surface of the protein, and polymorphisms in residues associated with recognition differences for the R proteins lead to significant changes in surface chemical properties. Analysis of single amino acid substitutions in AvrL567 proteins confirm the role of individual residues in conferring differences in recognition and suggest that the specificity results from the cumulative effects of multiple amino acid contacts. The structures also provide insights into possible pathogen-associated functions of AvrL567 proteins, with nucleic acid binding activity demonstrated in vitro. Our studies provide some of the first structural information on avirulence proteins that bind directly to the corresponding resistance proteins, allowing an examination of the molecular basis of the interaction with the resistance proteins as a step toward designing new resistance specificities. 相似文献
116.
The expression of rat brain voltage-sensitive Na+ channel mRNAs in Schwann cells was examined using in situ hybridization cytochemistry and RT-PCR. The mRNAs of rat brain Na+ channel subtype II and III, but not subtype I, were detected in cultured Schwann cells from sciatic nerve and in intact sciatic nerve, which contains Schwann cells but not neuronal cell bodies. These results indicate that rat brain Na+ channel mRNAs, which have been considered as mainly neuronal-type messages, are also expressed in glial cells in vitro and in vivo. 相似文献
117.
118.
Background
Metabolic reconstructions contain detailed information about metabolic enzymes and their reactants and products. These networks can be used to infer functional associations between metabolic enzymes. Many methods are based on the number of metabolites shared by two enzymes, or the shortest path between two enzymes. Metabolite sharing can miss associations between non-consecutive enzymes in a serial pathway, and shortest-path algorithms are sensitive to high-degree metabolites such as water and ATP that create connections between enzymes with little functional similarity. 相似文献119.
Dave JK Halldorsdottir VG Eisenbrey JR Raichlen JS Liu JB McDonald ME Dickie K Wang S Leung C Forsberg F 《American journal of physiology. Heart and circulatory physiology》2012,303(1):H126-H132
Right heart catheterization is often required to monitor intra-cardiac pressures in a number of disease states. Ultrasound contrast agents can produce pressure modulated subharmonic emissions that may be used to estimate right ventricular (RV) pressures. A technique based on subharmonic acoustic emissions from ultrasound contrast agents to track RV pressures noninvasively has been developed and its clinical potential evaluated. The subharmonic signals were obtained from the aorta, RV, and right atrium (RA) of five anesthetized closed-chest mongrel dogs using a SonixRP ultrasound scanner and PA4-2 phased array. Simultaneous pressure measurements were obtained using a 5-French solid state micromanometer tipped catheter. Initially, aortic subharmonic signals and systemic blood pressures were used to obtain a calibration factor in units of millimeters of mercury per decibel. This factor was combined with RA pressures (that can be obtained noninvasively) and the acoustic data from the RV to obtain RV pressure values. The individual calibration factors ranged from -2.0 to -4.0 mmHg/dB. The subharmonic signals tracked transient changes in the RV pressures within an error of 0.6 mmHg. Relative to the catheter pressures, the mean errors in estimating RV peak systolic and minimum diastolic pressures, and RV relaxation [isovolumic negative derivative of change in pressure over time (-dP/dt)] by use of the subharmonic signals, were -2.3 mmHg, -0.8 mmHg, and 2.9 mmHg/s, respectively. Overall, acoustic estimates of RV peak systolic and minimum diastolic pressures and RV relaxation were within 3.4 mmHg, 1.8 mmHg, and 5.9 mmHg/s, respectively, of the measured pressures. This pilot study demonstrates that subharmonic emissions from ultrasound contrast agents have the potential to noninvasively track in vivo RV pressures with errors below 3.5 mmHg. 相似文献
120.
In a series of batch experiments we compared the efficiencyof nitrogen regeneration of a two- and three-member microbialfood loop consisting of a mixed bacterial assemblage, a small(35 µm) heterotrophic flagellate (Paraphysomonassp.), and a large (712 µm) heterotrophic flagellate(Paraphysomonas imperforata). In the two-member system the nitrogenregeneration efficiency for NH4+ (Rn) was 41% and the grossgrowth efficiency (GGE) was 57% during active grazing by thesmall flagellate on bacteria. Regeneration of NH4+ continuedduring the stationary phase so that Rn was 75% after 6 daysincubation. When the larger flagellate was introduced at theend of exponential growth of the smaller grazer in the three-membersystem, initially there was rapid regrowth of bacteria, tyingup 15% of the nitrogen originally in the bacteria. The largerflagellate grazed the smaller one with a GGE of 55%. Total nitrogenregeneration efficiency through exponential growth of the largerflagellate was 73%. Because microbial food loops in naturalwaters are far more complicated and with more grazing stepsthan portrayed in this study, we would expect the bulk of nutrientswithin these systems to be recycled with little transfer tohigher trophic levels. 相似文献