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91.
Mayr JA Haack TB Graf E Zimmermann FA Wieland T Haberberger B Superti-Furga A Kirschner J Steinmann B Baumgartner MR Moroni I Lamantea E Zeviani M Rodenburg RJ Smeitink J Strom TM Meitinger T Sperl W Prokisch H 《American journal of human genetics》2012,90(2):314-320
Exome sequencing of an individual with congenital cataracts, hypertrophic cardiomyopathy, skeletal myopathy, and lactic acidosis, all typical symptoms of Sengers syndrome, discovered two nonsense mutations in the gene encoding mitochondrial acylglycerol kinase (AGK). Mutation screening of AGK in further individuals with congenital cataracts and cardiomyopathy identified numerous loss-of-function mutations in an additional eight families, confirming the causal nature of AGK deficiency in Sengers syndrome. The loss of AGK led to a decrease of the adenine nucleotide translocator in the inner mitochondrial membrane in muscle, consistent with a role of AGK in driving the assembly of the translocator as a result of its effects on phospholipid metabolism in mitochondria. 相似文献
92.
Nitschke Y Baujat G Botschen U Wittkampf T du Moulin M Stella J Le Merrer M Guest G Lambot K Tazarourte-Pinturier MF Chassaing N Roche O Feenstra I Loechner K Deshpande C Garber SJ Chikarmane R Steinmann B Shahinyan T Martorell L Davies J Smith WE Kahler SG McCulloch M Wraige E Loidi L Höhne W Martin L Hadj-Rabia S Terkeltaub R Rutsch F 《American journal of human genetics》2012,90(1):25-39
Spontaneous pathologic arterial calcifications in childhood can occur in generalized arterial calcification of infancy (GACI) or in pseudoxanthoma elasticum (PXE). GACI is associated with biallelic mutations in ENPP1 in the majority of cases, whereas mutations in ABCC6 are known to cause PXE. However, the genetic basis in subsets of both disease phenotypes remains elusive. We hypothesized that GACI and PXE are in a closely related spectrum of disease. We used a standardized questionnaire to retrospectively evaluate the phenotype of 92 probands with a clinical history of GACI. We obtained the ENPP1 genotype by conventional sequencing. In those patients with less than two disease-causing ENPP1 mutations, we sequenced ABCC6. We observed that three GACI patients who carried biallelic ENPP1 mutations developed typical signs of PXE between 5 and 8 years of age; these signs included angioid streaks and pseudoxanthomatous skin lesions. In 28 patients, no disease-causing ENPP1 mutation was found. In 14 of these patients, we detected pathogenic ABCC6 mutations (biallelic mutations in eight patients, monoallelic mutations in six patients). Thus, ABCC6 mutations account for a significant subset of GACI patients, and ENPP1 mutations can also be associated with PXE lesions in school-aged children. Based on the considerable overlap of genotype and phenotype of GACI and PXE, both entities appear to reflect two ends of a clinical spectrum of ectopic calcification and other organ pathologies, rather than two distinct disorders. ABCC6 and ENPP1 mutations might lead to alterations of the same physiological pathways in tissues beyond the artery. 相似文献
93.
Do HT Tselykh TV Mäkelä J Ho TH Olkkonen VM Bornhauser BC Korhonen L Zelcer N Lindholm D 《The Journal of biological chemistry》2012,287(16):12602-12611
94.
Nielsen AB Székely K Gath J Ernst M Nielsen NC Meier BH 《Journal of biomolecular NMR》2012,52(4):283-288
We present a scheme that allows the simultaneous detection of PAR and PAIN correlation spectra in a single two-dimensional
experiment. For both spectra, we obtain almost the same signal-to-noise ratio as if a PAR or PAIN spectrum is recorded separately,
which in turn implies that one of the spectra may be considered additional information for free. The experiment is based on
the observation that in a PAIN experiment, the PAR condition is always also fulfilled. The performance is demonstrated experimentally
using uniformly 13C,15N-labeled samples of N–f–MLF–OH and ubiquitin. 相似文献
95.
Gath J Habenstein B Bousset L Melki R Meier BH Böckmann A 《Biomolecular NMR assignments》2012,6(1):51-55
Parkinson’s disease is amongst the most frequent and most devastating neurodegenerative diseases. It is tightly associated
with the assembly of proteins into high-molecular weight protein species, which propagate between neurons in the central nervous
system. The principal protein involved in this process is α-synuclein which is a structural component of the Lewy bodies observed
in diseased brain. We here present the solid-state NMR sequential assignments of a new fibrillar form of this protein, the
first one with a well-ordered and rigid N-terminal part. 相似文献
96.
Evidence is growing for a role of Waddlia chondrophila as an agent of adverse pregnancy outcomes in both humans and ruminants. This emerging pathogen, member of the order Chlamydiales, is also implicated in bronchiolitis and lower respiratory tract infections. Until now, the serological diagnosis of W. chondrophila infection has mainly relied on manually intensive tests including micro-immunofluorescence and Western blotting. Thus, there is an urgent need to establish reliable high throughput serological assays. Using a combined genomic and proteomic approach, we detected 57 immunogenic proteins of W. chondrophila, of which 17 were analysed by mass spectrometry. Two novel hypothetical proteins, Wim3 and Wim4, were expressed as recombinant proteins in Escherichia coli, purified and used as antigens in an ELISA test. Both proteins were recognized by sera of rabbits immunized with W. chondrophila as well as by human W. chondrophila positive sera but not by rabbit pre-immune sera nor human W. chondrophila negative sera. These results demonstrated that the approach chosen is suitable to identify immunogenic proteins that can be used to develop a serological test. This latter will be a valuable tool to further clarify the pathogenic potential of W. chondrophila. 相似文献
97.
Chromatin is extensively chemically modified and thereby acts as a dynamic signaling platform controlling gene function. Chromatin regulation is integral to cell differentiation, lineage commitment and organism development, whereas chromatin dysregulation can lead to age-related and neurodegenerative disorders as well as cancer. Investigating chromatin biology presents a unique challenge, as the issue spans many disciplines, including cell and systems biology, biochemistry and molecular biophysics. In recent years, the application of chemical biology methods for investigating chromatin processes has gained considerable traction. Indeed, chemical biologists now have at their disposal powerful chemical tools that allow chromatin biology to be scrutinized at the level of the cell all the way down to the single chromatin fiber. Here we present recent examples of how this rapidly expanding palette of chemical tools is being used to paint a detailed picture of chromatin function in organism development and disease. 相似文献
98.
99.
100.
High variation in foliage and leaf litter chemistry among 45 tree species of a neotropical rainforest community 总被引:1,自引:0,他引:1
Distinct ecosystem level carbon : nitrogen : phosphorus (C : N : P) stoichiometries in forest foliage have been suggested to reflect ecosystem-scale selection for physiological strategies in plant nutrient use. Here, this hypothesis was explored in a nutrient-poor lowland rainforest in French Guiana. Variation in C, N and P concentrations was evaluated in leaf litter and foliage from neighbour trees of 45 different species, and the litter concentrations of major C fractions were also measured. Litter C ranged from 45.3 to 52.4%, litter N varied threefold (0.68-2.01%), and litter P varied seven-fold (0.009-0.062%) among species. Compared with foliage, mean litter N and P concentrations decreased by 30% and 65%, respectively. Accordingly, the range in mass-based N : P shifted from 14 to 55 in foliage to 26 to 105 in litter. Resorption proficiencies indicated maximum P withdrawal in most species, but with a substantial increase in variation in litter P compared with foliage. These data suggest that constrained ecosystem-level C : N : P ratios do not preclude the evolution of highly diversified strategies of nutrient use and conservation among tropical rainforest tree species. The resulting large variation in litter quality will influence stoichiometric constraints within the decomposer food web, with potentially far-ranging consequences on nutrient dynamics and plant-soil feedbacks. 相似文献