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71.
72.
Zeynep Kurkcuoglu Ahmet Bakan Duygu Kocaman Ivet Bahar Pemra Doruker 《PLoS computational biology》2012,8(9)
Catalytic loop motions facilitate substrate recognition and binding in many enzymes. While these motions appear to be highly flexible, their functional significance suggests that structure-encoded preferences may play a role in selecting particular mechanisms of motions. We performed an extensive study on a set of enzymes to assess whether the collective/global dynamics, as predicted by elastic network models (ENMs), facilitates or even defines the local motions undergone by functional loops. Our dataset includes a total of 117 crystal structures for ten enzymes of different sizes and oligomerization states. Each enzyme contains a specific functional/catalytic loop (10–21 residues long) that closes over the active site during catalysis. Principal component analysis (PCA) of the available crystal structures (including apo and ligand-bound forms) for each enzyme revealed the dominant conformational changes taking place in these loops upon substrate binding. These experimentally observed loop reconfigurations are shown to be predominantly driven by energetically favored modes of motion intrinsically accessible to the enzyme in the absence of its substrate. The analysis suggests that robust global modes cooperatively defined by the overall enzyme architecture also entail local components that assist in suitable opening/closure of the catalytic loop over the active site. 相似文献
73.
The Application of CRISPR/Cas Technology to Efficiently Model Complex Cancer Genomes in Stem Cells 下载免费PDF全文
Adam Albitar Bahar Rohani Brett Will Annie Yan G. Ian Gallicano 《Journal of cellular biochemistry》2018,119(1):134-140
CRISPR/Cas gene editing technologies have emerged as powerful tools in the study of oncogenic transformation. The system's specificity, versatility, and ease of implementation allow researchers to identify important molecular markers and pathways which grant cancers stem cell like properties. This technology has already been applied to researching specific cancers, but has seen restricted therapeutic applications due to inherent ethical and technical limitations. Active development and adaptation of the CRISPR/Cas system has produced new methods to take advantage of both non‐homologous end joining and homologous recombination repair mechanisms in attempts to remedy these limitations and improve the versatility of gene edits that can be created. Nonetheless, until issues with specificity and in vivo efficiency are resolved, utilization of CRISPR/Cas systems would be best employed in the modeling and study of various cancer genes. While it may have potential therapeutic applications to targeted cancer therapies in the future, presently CRISPR/Cas is a remarkable technique that can be utilized for easy and efficient gene editing when it comes to cancer research. J. Cell. Biochem. 119: 134–140, 2018. © 2017 Wiley Periodicals, Inc. 相似文献
74.
Jelani Ince 《Ethnic and racial studies》2018,41(8):1428-1434
This paper focuses on the contributions of Chris Lebron's book The Making of Black Lives Matter: The History of an Idea. Specifically, I examine his discussion of James Baldwin, Martin Luther King, Jr., and Audre Lorde and their opinions about love for their community, black self-actualization, and black liberation. I consider whether or not rage should play a role in our opinions about the #BlackLivesMatter movement and discuss whether or not it hurts the pursuit of freedom. I agree with the importance to look to the past in order to inform our political behaviour moving forward. Nonetheless, if we are to align with the #BlackLivesMatter movement, we must be willing to challenge what is often considered to be “proper” dissent. The review concludes with hypotheses about what black Americans should do as we work to reimagine a society where oppression is not integral to the maintenance of the American project. 相似文献
75.
RNA bulge entropies in the unbound state correlate with peptide binding strengths for HIV-1 and BIV TAR RNA because of improved conformational access. 下载免费PDF全文
For the binding of peptides to wild-type HIV-1 and BIV TAR RNA and to mutants with bulges of various sizes, changes in the DeltaDelta G values of binding were determined from experimental K d values. The corresponding entropies of these bulges are estimated by enumerating all possible RNA bulge conformations on a lattice and then applying the Boltzmann relationship. Independent calculations of entropies from fluctuations are also carried out using the Gaussian network model (GNM) recently introduced for analyzing folded structures. Strong correlations are seen between the changes in free energy determined for binding and the two different unbound entropy calculations. The fact that the calculated entropy increase with larger bulge size is correlated with the enhanced experimental binding free energy is unusual. This system exhibits a dependence on the entropy of the unbound form that is opposite to usual binding models. Instead of a large initial entropy being unfavorable since it would be reduced upon binding, here the larger entropies actually favor binding. Several interpretations are possible: (i) the higher conformational freedom implies a higher competence for binding with a minimal strain, by suitable selection amongst the set of already accessible conformations; (ii) larger bulge entropies enhance the probability of the specific favorable conformation of the bound state; (iii) the increased freedom of the larger bulges contri-butes more to the bound state than to the unbound state; (iv) indirectly the large entropy of the bound state might have an unfavorable effect on the solvent structure. Nonetheless, this unusual effect is interesting. 相似文献
76.
Persistent bacterial infections do not respond to current antibiotic treatments and thus present a great medical challenge. These conditions have been linked to the formation of dormant subpopulations of bacteria, known as persister cells, that are growth-arrested and highly tolerant to conventional antibiotics. Here, we report a new strategy of persister control and demonstrate that minocycline, an amphiphilic antibiotic that does not require active transport to penetrate bacterial membranes, is effective in killing Escherichia coli persister cells [by 70.8 ± 5.9% (0.53 log) at 100 μg/mL], while being ineffective in killing normal cells. Further mechanistic studies revealed that persister cells have reduced drug efflux and accumulate more minocycline than normal cells, leading to effective killing of this dormant subpopulation upon wake-up. Consistently, eravacycline, which also targets the ribosome but has a stronger binding affinity than minocycline, kills persister cells by 3 logs when treated at 100 μg/mL. In summary, the findings of this study reveal that while dormancy is a well-known cause of antibiotic tolerance, it also provides an Achilles’ heel for controlling persister cells by leveraging dormancy associated reduction of drug efflux. 相似文献
77.
78.
Mahbub Khandaker Rayhan Bahar Md Mezbaul Labbate Maurizio Krishnan Kannan Andrews Stuart Naidu Ravi Megharaj Mallavarapu 《Applied microbiology and biotechnology》2017,101(3):963-976
Applied Microbiology and Biotechnology - Contamination of land and water caused by heavy metal mercury (Hg) poses a serious threat to biota worldwide. The seriousness of toxicity of this neurotoxin... 相似文献
79.
Ince TA Ward JM Valli VE Sgroi D Nikitin AY Loda M Griffey SM Crum CP Crawford JM Bronson RT Cardiff RD 《Nature biotechnology》2008,26(9):978-9; discussion 979
80.
Fiona E. Matthews Carol Brayne James Lowe Ian McKeith Stephen B. Wharton Paul Ince 《PLoS medicine》2009,6(11)