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991.
Konings A Van Camp G Goethals A Van Eyken E Vandevelde A Ben Azza J Peeters N Wuyts W Smeets H Van Laer L 《Mitochondrion》2008,8(5-6):377-382
Specific mitochondrial DNA (mtDNA) mutations in 12SrRNA and tRNASer(UCN) cause non-syndromic hearing loss (NSHL). In this study, we screened 466 hearing loss (HL) patients, negative for GJB2 mutations, for mutations in the two mtDNA genes and flanking regions. In total, 43 different variants were identified, 31 of which were polymorphisms, one was a mutation (m.1555A-->G), two were known variants of controversial pathological nature (m.827A-->G and m.961delTinsC(n)) and nine were newly identified variants. The frequency of m.1555A-->G in this set of HL patients was 0.3%, which was lower than expected. To assess the putative causative nature of controversial or newly identified variants, the frequencies of these variants were determined in 400 Belgian control subjects, and their effect on the secondary structure and their conservation among different species was determined. Our data provide further support for a polymorphic nature of the controversial m.961delTinsC(n) variant. In addition, two of the newly identified variants, m.636A-->G in the 12SrRNA flanking tRNA(Phe) and m.990T-->C in 12SrRNA, may be new candidates for pathogenic HL variants. If the pathogenic nature of m.636A-->G can be confirmed, this would be the first NSHL mutation in tRNA(Phe). 相似文献
992.
993.
The Drosophila melanogaster multisubstrate deoxyribonucleoside kinase (dNK; EC 2.7.1.145) has a high turnover rate and a wide substrate range that makes it a very good candidate for gene therapy. This concept is based on introducing a suicide gene into malignant cells in order to activate a prodrug that eventually may kill the cell. To be able to optimize the function of dNK, it is vital to have structural information of dNK complexes. In this study we present crystal structures of dNK complexed with four different nucleoside analogs (floxuridine, brivudine, zidovudine and zalcitabine) and relate them to the binding of substrate and feedback inhibitors. dCTP and dGTP bind with the base in the substrate site, similarly to the binding of the feedback inhibitor dTTP. All nucleoside analogs investigated bound in a manner similar to that of the pyrimidine substrates, with many interactions in common. In contrast, the base of dGTP adopted a syn-conformation to adapt to the available space of the active site. 相似文献
994.
Sun X Wiesner B Lorenz D Papsdorf G Pankow K Wang P Dietrich N Siems WE Maul B 《Biological chemistry》2008,389(12):1477-1485
Angiotensin-converting enzyme (ACE) demonstrates, besides its typical dipeptidyl-carboxypeptidase activity, several unusual functions. Here, we demonstrate with molecular, biochemical, and cellular techniques that the somatic wild-type murine ACE (mACE), stably transfected in Chinese Hamster Ovary (CHO) or Madin-Darby Canine Kidney (MDCK) cells, interacts with endogenous membranal co-localized carboxypeptidase M (CPM). CPM belongs to the group of glycosylphosphatidylinositol (GPI)-anchored proteins. Here we report that ACE, completely independent of its known dipeptidase activities, has GPI-targeted properties. Our results indicate that the spatial proximity between mACE and the endogenous CPM enables an ACE-evoked release of CPM. These results are discussed with respect to the recently proposed GPI-ase activity and function of sperm-bound ACE. 相似文献
995.
Linda Engblom Lena Eliasson-Selling Nils Lundeheim Katinka Belák Kjell Andersson Anne-Marie Dalin 《Acta veterinaria Scandinavica》2008,50(1):25
Background
The aim of this study was to get information on post mortem diagnoses of sows found dead or euthanised and to understand the diagnoses aetiology (causative background). Moreover, the study was to evaluate the association between the clinical symptoms observed on farm and post mortem findings. 相似文献996.
997.
Nils T. Hagen 《PloS one》2008,3(12)
Authorship credit for multi-authored scientific publications is routinely allocated either by issuing full publication credit repeatedly to all coauthors, or by dividing one credit equally among all coauthors. The ensuing inflationary and equalizing biases distort derived bibliometric measures of merit by systematically benefiting secondary authors at the expense of primary authors. Here I show how harmonic counting, which allocates credit according to authorship rank and the number of coauthors, provides simultaneous source-level correction for both biases as well as accommodating further decoding of byline information. I also demonstrate large and erratic effects of counting bias on the original h-index, and show how the harmonic version of the h-index provides unbiased bibliometric ranking of scientific merit while retaining the original''s essential simplicity, transparency and intended fairness. Harmonic decoding of byline information resolves the conundrum of authorship credit allocation by providing a simple recipe for source-level correction of inflationary and equalizing bias. Harmonic counting could also offer unrivalled accuracy in automated assessments of scientific productivity, impact and achievement. 相似文献
998.
Schrohl AS Würtz S Kohn E Banks RE Nielsen HJ Sweep FC Brünner N 《Molecular & cellular proteomics : MCP》2008,7(10):2061-2066
With the increasing demand of providing personalized medicine the need for biobanking of biological material from individual patients has increased. Such samples are essential for molecular research aimed at characterizing diseases at several levels ranging from epidemiology and diagnostic and prognostic classification to prediction of response to therapy. Clinically validated biomarkers may provide information to be used for diagnosis, screening, evaluation of risk/predisposition, assessment of prognosis, monitoring (recurrence of disease), and prediction of response to treatment and as a surrogate response marker. Many types of biological fluids or tissues can be collected and stored in biorepositories. Samples of blood can be further processed into plasma and serum, and tissue pieces can be either frozen or fixed in formalin and then embedded into paraffin. The present review focuses on biological fluids, especially serum and plasma, intended for study of protein biomarkers. In biomarker studies the process from the decision to take a sample from an individual to the moment the sample is safely placed in the biobank consists of several phases including collection of samples, transport of the samples, and handling and storage of samples. Critical points in each step important for high quality biomarker studies are described in this review. Failure to develop and adhere to robust standardized protocols may have significant consequences as the quality of the material stored in the biobank as well as conclusions and clinical recommendations based on analysis of such material may be severely affected. 相似文献
999.
1000.
Growth in mammals often implies differences in body proportions and tissue development more or less characteristic for different
age periods and ontogenetic stages. Mouth morphology is an important functional trait in herbivores, as it may determine both
maximal intake rate and possibly level of selectivity. An untested hypothesis is that since individual bones within the skeleton
are retarded in growth and development in proportion to their growth intensity at each time interval during periods of restricted
nutritional supply, this may potentially affect ultimate skeletal proportions. We analysed data on mandible proportions (anterior:total)
of 62 fetuses collected at different stages of growth and 16 776 red deerCervus elaphus Linnaeus, 1758 hinds from 0 to 26 years of age and 24026 males from 0 to 22 years of age harvested during autumns 1965–2001
along the west coast of Norway. At the fetal stage, the mandible proportion was negatively related to body weight and, therefore,
declined with age of the fetus. The anterior part of the mandible was initially longer than the posterior part; the mandible
proportion was between 0.75–0.8 at the fetal stage, but declined with increasing age. The relationship between mandible proportion
and weight was strong for calves, but decreased with increasing age, and the relationship was almost flat when reaching 5
years of age. From 5 years, the anterior and posterior part of the mandible was approximately equal in length and this mandible
proportion (0.50–0.51), which was unrelated to weight, remained stable for the rest of the life in both hinds and stags. After
they were fully-grown, early conditions (cohort density and climate as measured by the North Atlantic Oscillation) had no
measurable effect on ultimate mandible proportions after the effect of body weight was removed. 相似文献