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排序方式: 共有264条查询结果,搜索用时 20 毫秒
31.
Tucker DC Acton RT Press N Ruggiero A Reiss JA Walker AP Wenzel L Harrison B Fadojutimi-Akinsiku M Harrison H Adams P Crabb JA Anderson R Thomson E 《Genetic testing》2006,10(1):50-59
We queried 101,951 white, Hispanic, black, Asian, American Indian (i.e., American Indian or Alaska Native in the United States and North American Indian, Metis, or Inuit in Canada) and Pacific Islander (including Native Hawaiian) adults who agreed to be genotypically and phenotypically screened for hemochromatosis as part of the Hemochromatosis and Iron Overload Screening (HEIRS) study about their views on sharing genetic test information with family members. Multiple logistic regression (adjusting for study site, age group, race/ethnicity, preferred language, gender, education group, income group, SF-36 General Health and Mental Health subscales, perceived benefits and limitations of genetic testing, and belief that genetic testing is a good idea) evaluated independent predictors of responding "Strongly Agree" or "Agree" versus "Disagree" or "Strongly Disagree" to the statement "Information about a person's genetic risk should be shared with family members". Agreement that genetic risk information should be shared with family members was high (93% in the overall sample of 78,952 who answered this question), but differed among racial/ethnic groups. Hispanics were significantly less likely to agree that genetic test information should be shared with family members (i.e., 88% versus 92% or more among all other ethnicities). The relationship of perceived limitations and benefits of testing, gender, and age group to the belief that information should be shared differed among racial/ethnic groups, with Spanish-preferring Hispanics being the most different from other subgroups. 相似文献
32.
I Bruce M Akhlaq GC Bloomfield E Budd B Cox B Cuenoud P Finan P Gedeck J Hatto JF Hayler D Head T Keller L Kirman C Leblanc DL Grand C McCarthy D O'Connor C Owen MS Oza G Pilgrim NE Press L Sviridenko L Whitehead 《Bioorganic & medicinal chemistry letters》2012,22(17):5445-5450
Using a parallel synthesis approach to target a non-conserved region of the PI3K catalytic domain a pan-PI3K inhibitor 1 was elaborated to provide alpha, delta and gamma isoform selective Class I PI3K inhibitors 21, 24, 26 and 27. The compounds had good cellular activity and were selective against protein kinases and other members of the PI3K superfamily including mTOR and DNA-PK. 相似文献
33.
Fine mapping of a seizure susceptibility locus on mouse Chromosome 1: nomination of Kcnj10 as a causative gene 总被引:2,自引:2,他引:0
Thomas N. Ferraro Gregory T. Golden George G. Smith James F. Martin Falk W. Lohoff Tracy A. Gieringer Deborah Zamboni Candice L. Schwebel Danielle M. Press Stephanie Hongyu O. KratzerZhao Wade H. Berrettini Russell J. Buono 《Mammalian genome》2004,15(4):239-251
Previous quantitative trait loci (QTL) mapping studies document that the distal region of mouse Chromosome (Chr) 1 contains a gene(s) that is in large part responsible for the difference in seizure susceptibility between C57BL/6 (B6) (relatively seizure-resistant) and DBA/2 (D2) (relatively seizure-sensitive) mice. We now confirm this seizure-related QTL (Szs1) using reciprocal, interval-specific congenic strains and map it to a 6.6-Mb segment between Pbx1 and D1Mit150. Haplotype conservation between strains within this segment suggests that Szs1 may be localized more precisely to a 4.1-Mb critical interval between Fcgr3 and D1Mit150. We compared the coding region sequences of candidate genes between B6 and D2 mice using RT-PCR, amplification from genomic DNA, and database searching and discovered 12 brain-expressed genes with SNPs that predict a protein amino acid variation. Of these, the most compelling seizure susceptibility candidate is Kcnj10. A survey of the Kcnj10 SNP among other inbred mouse strains revealed a significant effect on seizure sensitivity such that most strains possessing a haplotype containing the B6 variant of Kcnj10 have higher seizure thresholds than those strains possessing the D2 variant. The unique role of inward-rectifying potassium ion channels in membrane physiology coupled with previous strong association between ion channel gene mutations and seizure phenotypes puts even greater focus on Kcnj10 in the present model. In summary, we confirmed a seizure-related QTL of large effect on mouse Chr 1 and mapped it to a finely delimited region. The critical interval contains several candidate genes, one of which, Kcnj10, exhibits a potentially important polymorphism with regard to fundamental aspects of seizure susceptibility. 相似文献
34.
Allan S. Hoffman Patrick S. Stayton Oliver Press Niren Murthy Chantal A. Lackey Charles Cheung Fiona Black Jean Campbell Nelson Fausto Themis R. Kyriakides Paul Bornstein 《Biotechnology and Bioprocess Engineering》2001,6(4):205-212
One of the important characteristics of biological systems is their ability to change important properties in response to
small environmental signals. The molecular mechanisms that biological molecules utilize to sense and respond provide interesting
models for the development of “smart” polymeric biomaterials with biomimetic properties. An important example of this is the
protein coat of viruses, which contains peptide units that facilitate the trafficking of the virus into the cell via endocytosis,
then out of the endosome into the cytoplasm, and from there into the nucleus. We have designed a family of synthetic polymers
whose compositions have been designed to mimic specific peptides on viral coats that facilitate endosomal escape. Our biomimetic
polymers are responsive to the lowered pH within endosomes, leading to disruption of the endosomal membrane and release of
important biomolecular drugs such as DNA, RNA, peptides and proteins to the cytoplasm before they are trafficked to lysosomes
and degraded by lysosomal enzymes. In this article, we review our work on the design, synthesis and action of such smart,
pH-sensitive polymers. 相似文献
35.
The N- and C-terminal amino acid sequences of the heavy chain from a pathological human immunoglobulin IgG 总被引:50,自引:33,他引:17
The heavy chain of a pathological human immunoglobulin IgG and also the Fd fragment have been isolated. No free alpha-amino group was present on either and the N-terminal sequence of both has been identified as pyrrolid-2-one-5-carbonylvalylthreonine. Splitting at the four methionine residues of the heavy chain with cyanogen bromide gave five fractions. The fraction from the C-terminal end of the chain was isolated in high yield and the amino acid sequence was: His-Glu-Ala-Leu-His-Asp(NH(2))-His-Tyr-Thr-Glu(NH(2))-Lys-Ser-Leu-Ser-Leu-Ser-Pro-Gly These results give strong support to the view that the heavy chain of immunoglobulin is a single peptide chain. 相似文献
36.
Brian M.O. Ogendi Rakesh K. Bakshi Kanupriya Gupta Richa Kapil LaDraka T. Brown Stephen J. Jordan Steffanie Sabbaj Christen G. Press Jeannette Y. Lee William M. Geisler 《Microbes and infection / Institut Pasteur》2018,20(3):176-184
T cell phenotypes involved in the immune response to Chlamydia trachomatis (CT) have not been fully elucidated in humans. We evaluated differences in T cell phenotypes between CT-infected women and CT-seronegative controls and investigated changes in T cell phenotype distributions after CT treatment and their association with reinfection. We found a higher expression of T cell activation markers (CD38+HLA-DR+), T helper type 1 (Th1)- and Th2-associated effector phenotypes (CXCR3+CCR5+ and CCR4+, respectively), and T cell homing marker (CCR7) for both CD4+ and CD8+ T cells in CT-infected women. At follow-up after treatment of infected women, there were a lower proportion of CD4+ and CD8+ T cells expressing these markers. These findings suggest a dynamic interplay of CD4+ and CD8+ T cells in CT infection, and once the infection is treated, these cell markers return to basal expression levels. In women without reinfection, a significantly higher proportion of CD8+ T cells co-expressing CXCR3 with CCR5 or CCR4 at follow-up was detected compared to women with reinfection, suggesting they might play some role in adaptive immunity. Our study elucidated changes in T cell phenotypes during CT infection and after treatment, broadening our understanding of adaptive immune mechanisms in human CT infections. 相似文献
37.
Upland rice (Oryza sativa L.) was grown at both ambient (350 μmol mol?1) and elevated (700 μmol mol?1) CO2 in either the presence or absence of the root hemi‐parasitic angiosperm Striga hermonthica (Del) Benth. Elevated CO2 alleviated the impact of the parasite on host growth: biomass of infected rice grown at ambient CO2 was 35% that of uninfected, control plants, while at elevated CO2, biomass of infected plants was 73% that of controls. This amelioration occurred despite the fact that O. sativa grown at elevated CO2 supported both greater numbers and a higher biomass of parasites per host than plants grown at ambient CO2. The impact of infection on host leaf area, leaf mass, root mass and reproductive tissue mass was significantly lower in plants grown at elevated as compared with ambient CO2. There were significant CO2 and Striga effects on photosynthetic metabolism and instantaneous water‐use efficiency of O. sativa. The response of photosynthesis to internal [CO2] (A/Ci curves) indicated that, at 45 days after sowing (DAS), prior to emergence of the parasites, uninfected plants grown at elevated CO2 had significantly lower CO2 saturated rates of photosynthesis, carboxylation efficiencies and ribulose‐1,5‐bisphosphate carboxylase/oxygenase (Rubisco; EC 4.1.1.39) contents than uninfected, ambient CO2‐grown O. sativa. In contrast, infection with S. hermonthica prevented down‐regulation of photosynthesis in O. sativa grown at elevated CO2, but had no impact on photosynthesis of hosts grown at ambient CO2. At 76 DAS (after parasites had emerged), however, infected plants grown at both elevated and ambient CO2 had lower carboxylation efficiencies and Rubisco contents than uninfected O. sativa grown at ambient CO2. The reductions in carboxylation efficiency (and Rubisco content) were accompanied by similar reductions in nitrogen concentration of O. sativa leaves, both before and after parasite emergence. There were no significant CO2 or infection effects on the concentrations of soluble sugars in leaves of O. sativa, but starch concentration was significantly lower in infected plants at both CO2 concentrations. These results demonstrate that elevated CO2 concentrations can alleviate the impact of infection with Striga on the growth of C3 hosts such as rice and also that infection can delay the onset of photosynthetic down‐regulation in rice grown at elevated CO2. 相似文献
38.
Jinbiao Zhan Patrick Stayton Oliver W. Press 《Cancer immunology, immunotherapy : CII》1998,46(1):55-60
A pKK expression system in Escherichia coli was used to produce recombinant ricin A chain (rRTA) and rRTA modified by addition
of organelle-specific amino acid retention sequences, including KDEL (an endoplasmic reticulum, ER, lumen retention signal),
KKMP (an ER membrane retention signal), YQRL (a trans-Golgi network retention signal) and KFERQ (a lysosome-targeting signal)
to the C terminus of rRTA. The toxicities of these RTA mutants were assessed in Jurkat cells following fluid-phase endocytosis.
rRTA-KDEL and rRTA-YQRL were significantly more cytotoxic for Jurkat cells than rRTA, rRTA-KKMP or rRTA-KFERQ. This difference
did not result from signal(KDEL or YQRL)-mediated binding of these RTA mutants to the cell surface. Reconstituted ER and Golgi
vesicles have been employed to assess translocation of rRTA and mutant rRTA. RTA-KDEL and RTA-YQRL respectively exhibited
6.7-fold and 6.1-fold more protection against papain digestion in reconstituted ER vesicles and 2.2-fold and 1.8-fold more
protection in reconstituted Golgi vesicles, than unmodified rRTA. These mutants were reassociated with ricin B chain to form
holotoxins. The mutant RTA-KDEL and RTA-YQRL holotoxins were 3.8-fold and 1.5-fold more cytotoxic for target cells, respectively,
than ricin produced using unmodified rRTA. Our results suggest that both ER and the trans-Golgi network may play important
roles in the intracellular trafficking and translocation of ricin A chain.
Received: 14 August 1997 / Accepted: 14 October 1997 相似文献
39.
Amiloride does not alter NaCl avoidance in Fischer-344 rats 总被引:2,自引:2,他引:0
Fischer-344 (F-344) rats differ from other common rat strains in that they
fail to show any preference for NaCl at any concentration in two- bottle
preference tests. Because 100 microM amiloride partially blocks the
NaCl-evoked chorda tympani (CT) response in electrophysiological studies,
we tested NaCl preference (0.068-0.273 M) in F-344 rats with and without
100 microM amiloride solution as the solvent. A third group was tested with
unadulterated NaCl solutions following CT transection. Amiloride had no
significant effect on the NaCl preference-aversion function, whereas CT
transection significantly reduced NaCl avoidance. These results suggest
that the amiloride-sensitive component of the NaCl response is not
necessary for F-344 rats to display avoidance of NaCl, but the entire CT
input is.
相似文献
40.