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51.
We have analyzed nucleotide polymorphism within a 5.3-kb region encompassing the functional Est-6 gene and the psiEst-6 putative pseudogene in 28 strains of Drosophila melanogaster and one of D. simulans. Two divergent sequence types were detected, which are not perfectly associated with Est-6 allozyme variation. The level of variation (pi) is very close in the 5'-flanking region (0.0059) and Est-6 gene (0.0057), but significantly higher in the intergenic region (0.0141) and putative pseudogene (0.0122). The variation in the 3'-flanking region is intermediate (0.0083). These observations may reflect different levels of purifying selection in the different regions. Strong linkage disequilibrium occurs within the region studied, with the largest values revealed in the putative pseudogene and 3'-flanking region. Moreover, recombination is restricted within psiEst-6. Gene conversion is detected both within and (to a lesser extent) between Est-6 and psiEst-6. The data indicate that psiEst-6 exhibits some characteristics that are typical of nonfunctional genes, while other characteristics are typically attributed to functional genes; the same situation has been observed in other pseudogenes (including Drosophila). The results of structural entropy analysis demonstrate higher structural ordering in Est-6 than in psiEst-6, in accordance with expectations if psiEst-6 is indeed a pseudogene. Taking into account that the function of psiEst-6 is not known (but could exist) and following the terminology of J. Brosius and S. J. Gould, we suggest that the term "potogene" may be appropriate for psiEst-6, indicating that it is a potential gene that may have acquired some distinctive but unknown function. 相似文献
52.
Circadian variation of serum leptin in healthy and diabetic men 总被引:18,自引:0,他引:18
Kanabrocki EL Hermida RC Wright M Young RM Bremner FW Third JL Ryan MD Ayala DE Johnson M Nemchausky BA Shirazi P Scheving LE Olwin JH 《Chronobiology international》2001,18(2):273-283
Leptin, from the Greek leptos, meaning thin (in reference to its ability to reduce body fat stores), is a hormone secreted primarily by adipocytes. At one time, leptin was portrayed as a potential means of combating obesity. Recently, leptin has been identified as a potent inhibitor of bone formation, acting through the central nervous system. Since numerous studies clearly show that bone remodeling is circadian rhythmic with peak activity during sleep, it is of interest to explore circadian variability in serum leptin. Accordingly, circadian characteristics of serum leptin were examined in 7 clinically healthy men and 4 obese men with type II diabetes. Blood samples were collected for 24 h at 3 h intervals beginning at 19:00. The dark (sleep) phase of the light-dark cycle extended from 22:30 to 06:30, with brief awakening for sampling at 01:00 and 04:00. Subjects consumed general hospital meals (2400 calories) at 16:30, 07:30, and 13:30. Serum leptin levels were determined by a R&D Systems enzyme immunoassay technique. Data were analyzed by linear least-squares estimation using the population multiple components method. A statistically significant (P < .018) circadian rhythm modeled by a single 24 h cosine curve characterized the data of each group. The 24 h mean leptin level was statistically greater (P < .001) in the obese diabetic men than in the healthy men (9.47 +/- 0.66 ng/mL vs. 24.07 +/- 1.71 ng/mL, respectively). Higher leptin levels occurred between midnight and roughly 02:30, and lowest leptin levels occurred between noon and the early afternoon. The phasing of this rhythm is similar to the circadian rhythm in bone remodeling previously described. Our results suggest the findings from a single morning blood sampling for leptin may be misleading since it may underestimate the mean 24 h and peak concentrations of the hormone. 相似文献
53.
A novel founder mutation in the RNASEL gene, 471delAAAG,is associated with prostate cancer in Ashkenazi Jews 总被引:7,自引:0,他引:7
Rennert H Bercovich D Hubert A Abeliovich D Rozovsky U Bar-Shira A Soloviov S Schreiber L Matzkin H Rennert G Kadouri L Peretz T Yaron Y Orr-Urtreger A 《American journal of human genetics》2002,71(4):981-984
HPC1/RNASEL was recently identified as a candidate gene for hereditary prostate cancer. We identified a novel founder frameshift mutation in RNASEL, 471delAAAG, in Ashkenazi Jews. The mutation frequency in the Ashkenazi population, estimated on the basis of the frequency in 150 healthy young women, was 4% (95% confidence interval [CI] 1.9%-8.4%). Among Ashkenazi Jews, the mutation frequency was higher in patients with prostate cancer (PRCA) than in elderly male control individuals (6.9% vs. 2.4%; odds ratio = 3.0; 95% CI 0.6-15.3; P=.17). 471delAAAG was not detected in the 134 non-Ashkenazi patients with PRCA and control individuals tested. The median age at PRCA diagnosis did not differ significantly between the Ashkenazi carriers and noncarriers included in our study. However, carriers received diagnoses at a significantly earlier age, compared with patients with PRCA who were registered in the Israeli National Cancer Registry (65 vs. 74.4 years, respectively; P<.001). When we examined two brothers with PRCA, we found a heterozygous 471delAAAG mutation in one and a homozygous mutation in the other. Loss of heterozygosity was demonstrated in the tumor of the heterozygous sib. Taken together, these data suggest that the 471delAAAG null mutation is associated with PRCA in Ashkenazi men. However, additional studies are required to determine whether this mutation confers increased risk for PRCA in this population. 相似文献
54.
Martínez de Villarreal L Pérez JZ Vázquez PA Herrera RH Campos Mdel R López RA Ramírez JL Sánchez JM Villarreal JJ Garza MT Limón A López AG Bárcenas M García JR Domínguez AS Nuñez RH Ayala JL Martínez JG González MT Alvarez CG Castro RN 《Teratology》2002,66(5):249-256
BACKGROUND: Nuevo León is a state in northeastern Mexico, near the border of Texas. Mean mortality rate from 1996-98 due to anencephaly cases was 0.6/1,000. In 1999 a surveillance program for the registry and prevention of neural tube defects (NTD) cases was initiated. METHODS: Cases were obtained from hospitals and OB-GYN clinics by immediate notification, death certificates, or fetal death registries. Only isolated cases of NTD were included. In August 1999 a folic acid campaign was initiated with the free distribution of the vitamin to low-income women with a recommendation to take a 5.0-mg pill once a week. Number of cases and rates from 1999 to 2001 were compared (chi(2) test). RESULTS: After 2 years there has been a significant reduction in the number of cases and rates. In 1999 there were 95 NTD cases and in the years 2000 and 2001 there were only 59 and 55 respectively (P < 0.001). NTD rate decreased from 1.04/1,000 in 1999 to 0.58/1,000 in 2001. Anencephaly and spina bifida rates decreased from 0.55/1,000 to 0.29/1,000 and from 0.47/1,000 to 0.22/1,000 respectively, from 1999-2001. Decrease of female cases was higher than male cases for both phenotypes. CONCLUSION: After 2 years there was a 50% decrease in the incidence of anencephaly and spina bifida cases with a significant reduction of infant mortality and disability. These results encourage us to propose the use of a single tablet of 5.0-mg of folic acid per week as an alternative to supplementation on a daily basis. 相似文献
55.
56.
B. Michalzik E. Tipping J. Mulder J.F. Gallardo Lancho E. Matzner C.L. Bryant N. Clarke S. Lofts M.A. Vicente Esteban 《Biogeochemistry》2003,66(3):241-264
DyDOC describes soil carbon dynamics, with a focus on dissolved organic carbon (DOC). The model treats the soil as a three-horizon profile, and simulates metabolic carbon transformations, sorption reactions and water transport. Humic substances are partitioned into three fractions, one of which is immobile, while the other two (hydrophilic and hydrophobic) can pass into solution as DOC. DyDOC requires site-specific soil characteristics, and is driven by inputs of litter and water, and air and soil temperatures. The model operates on hourly and daily time steps, and can simulate carbon cycling over both long (hundreds-to-thousands of years) and short (daily) time scales. An important feature of DyDOC is the tracking of 14C, from its entry in litter to its loss as DO14C in drainage water, enabling information about C dynamics to be obtained from both long-term radioactive decay, and the characteristic 14C pulse caused by thermonuclear weapon testing during the 1960s ("bomb carbon"). Parameterisation is performed by assuming a current steady state. Values of a range of variables, including C pools, annual DOC fluxes, and 14C signals, are combined into objective functions for least-squares minimisation. DyDOC has been applied successfully to spruce forest sites at Birkenes (Norway) and Waldstein (Germany), and most of the parameters have similar values at the two sites. The results indicate that the supply of DOC from the surface soil horizon to percolating water depends upon the continual metabolic production of easily leached humic material. In contrast, concentrations and fluxes of DOC in the deeper soil horizons are controlled by sorption processes, involving comparatively large pools of leachable organic matter. Times to reach steady state are calculated to be several hundred years in the organic layer, and hundreds-to-thousands of years in the deeper mineral layers. It is estimated that DOC supplies 89% of the mineral soil carbon at Birkenes, and 73% at Waldstein. The model, parameterised with "steady state" data, simulates short-term variations in DOC concentrations and fluxes, and in DO14C, which are in approximate agreement with observations. 相似文献
57.
Zlotorynski E Rahat A Skaug J Ben-Porat N Ozeri E Hershberg R Levi A Scherer SW Margalit H Kerem B 《Molecular and cellular biology》2003,23(20):7143-7151
Fragile sites are specific loci that form gaps, constrictions, and breaks on chromosomes exposed to partial replication stress and are rearranged in tumors. Fragile sites are classified as rare or common, depending on their induction and frequency within the population. The molecular basis of rare fragile sites is associated with expanded repeats capable of adopting unusual non-B DNA structures that can perturb DNA replication. The molecular basis of common fragile sites was unknown. Fragile sites from R-bands are enriched in flexible sequences relative to nonfragile regions from the same chromosomal bands. Here we cloned FRA7E, a common fragile site mapped to a G-band, and revealed a significant difference between its flexibility and that of nonfragile regions mapped to G-bands, similar to the pattern found in R-bands. Thus, in the entire genome, flexible sequences might play a role in the mechanism of fragility. The flexible sequences are composed of interrupted runs of AT-dinucleotides, which have the potential to form secondary structures and hence can affect replication. These sequences show similarity to the AT-rich minisatellite repeats that underlie the fragility of the rare fragile sites FRA16B and FRA10B. We further demonstrate that the normal alleles of FRA16B and FRA10B span the same genomic regions as the common fragile sites FRA16C and FRA10E. Our results suggest that a shared molecular basis, conferred by sequences with a potential to form secondary structures that can perturb replication, may underlie the fragility of rare fragile sites harboring AT-rich minisatellite repeats and aphidicolin-induced common fragile sites. 相似文献
58.
The origin of antigenic diversity in Plasmodium falciparum 总被引:3,自引:0,他引:3
Most studies of genetic variability of Plasmodium falciparum have focused on protein antigens and the genes that encode them. The consensus is that populations exhibit high levels of genetic polymorphism, most notably the genes encoding surface proteins of the merozoite (Msp1, Msp2) and the sporozoite (Csp). The age and derivation of this variation is a subject that warrants further careful consideration, as discussed here by Stephen Rich, Marcelo Ferreira and Francisco Ayala. 相似文献
59.
Mutation of W215 compromises thrombin cleavage of fibrinogen, but not of PAR-1 or protein C 总被引:3,自引:0,他引:3
W215 is a highly conserved residue that shapes the S3 and S4 specificity sites of thrombin and participates in an edge-to-face interaction with residue F8 of the fibrinogen Aalpha chain. Protein C and the platelet receptor PAR-1 carry an acidic residue at P3 and bind to the active site of thrombin without making contact with W215. This suggested that mutation of W215 could dissociate the cleavage of fibrinogen from that of protein C and PAR-1. Replacement of W215 with Phe produces modest effects on thrombin function, whereas the W215Y replacement compromises significantly the catalytic activity toward all chromogenic and natural substrates that are tested. Replacement of W215 with Ala almost obliterates Na(+) binding, reduces the level of fibrinogen cleavage 500-fold, but decreases the levels of protein C activation and PAR-1 cleavage only 3- and 25-fold, respectively. The W215A mutant cleaves PAR-1 with a specificity constant that is more than 13-fold higher than that of fibrinogen and protein C and is the first thrombin derivative to be described that functions as an almost exclusive activator of PAR-1. The environment of W215 influences differentially three physiologically important interactions of thrombin, which should assist in the study of each of these functions separately in vivo. 相似文献
60.
Smith DS Niethammer M Ayala R Zhou Y Gambello MJ Wynshaw-Boris A Tsai LH 《Nature cell biology》2000,2(11):767-775
Whereas total loss of Lis1 is lethal, disruption of one allele of the Lis1 gene results in brain abnormalities, indicating that developing neurons are particularly sensitive to a reduction in Lis1 dosage. Here we show that Lis1 is enriched in neurons relative to levels in other cell types, and that Lis1 interacts with the microtubule motor cytoplasmic dynein. Production of more Lis1 in non-neuronal cells increases retrograde movement of cytoplasmic dynein and leads to peripheral accumulation of microtubules. These changes may reflect neuron-like dynein behaviours induced by abundant Lis1. Lis1 deficiency produces the opposite phenotype. Our results indicate that abundance of Lis1 in neurons may stimulate specific dynein functions that function in neuronal migration and axon growth. 相似文献