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941.
942.
Yip KY Patel P Kim PM Engelman DM McDermott D Gerstein M 《Bioinformatics (Oxford, England)》2008,24(2):290-292
Residue coevolution has recently emerged as an important concept, especially in the context of protein structures. While a multitude of different functions for quantifying it have been proposed, not much is known about their relative strengths and weaknesses. Also, subtle algorithmic details have discouraged implementing and comparing them. We addressed this issue by developing an integrated online system that enables comparative analyses with a comprehensive set of commonly used scoring functions, including Statistical Coupling Analysis (SCA), Explicit Likelihood of Subset Variation (ELSC), mutual information and correlation-based methods. A set of data preprocessing options are provided for improving the sensitivity and specificity of coevolution signal detection, including sequence weighting, residue grouping and the filtering of sequences, sites and site pairs. A total of more than 100 scoring variations are available. The system also provides facilities for studying the relationship between coevolution scores and inter-residue distances from a crystal structure if provided, which may help in understanding protein structures. AVAILABILITY: The system is available at http://coevolution.gersteinlab.org. The source code and JavaDoc API can also be downloaded from the web site. 相似文献
943.
Warwick RM Rushambuza FG Brown J Patel R Tabb S Poniatowski S Ranson AJ Brown CJ 《Cell and tissue banking》2008,9(4):323-328
Blood samples collected from deceased tissue donors for mandatory transfusion microbiology testing may be taken either at
the time of tissue donation, or residual samples may be retrieved from hospital laboratories where they were originally used
for ante-mortem tests. In the latter case, sample labelling may not conform to the required standard, which stipulates that
three independent identifiers be provided. If no alternative adequately labelled sample is available for testing the donated
tissues may have to be discarded, which can adversely affect tissue sufficiency. An alternative method to ensure that the
blood sample to be tested is from the intended deceased donor is to confirm the identity of the blood sample by Deoxyribonucleic
Nucleic Acid (DNA) Short Tandem Repeats (STR) analysis, then comparing the DNA profile with the DNA from the donated tissues.
If the two DNA profiles are identical, probability calculations can demonstrate the chance of the two samples of DNA being
from the same or different individuals. The authors have used this approach to salvage deceased tissue donations. 相似文献
944.
Bakshi SR Dave BJ Sanger W Brahmbhatt MM Trivedi PJ Kakadia PM Patel SJ 《Cytogenetic and genome research》2008,121(1):14-17
Cytogenetic analysis in peripheral blood lymphocytes of a 50-year-old female with tongue cancer showed the presence of one to three copies of a small supernumerary marker chromosome (sSMC) in a mosaic state. Family studies also revealed the marker in mosaic form in four (age <29 years) of eleven clinically normal individuals studied from her family of 16 individuals spanning three generations. Due to the extremely small size of the marker chromosome, identification by classical cytogenetics was not informative. Multicolor FISH followed by whole chromosome painting identified the marker as a derivative of chromosome 21. This is the first report of sSMC21 in an adult-onset tongue cancer patient and some of her family members with no clinical symptoms. 相似文献
945.
The main aim of the present study was to evaluate potential of ternary complexation (comprising of drug, cyclodextrin and
polymer) as an approach for taste masking. For this purpose famotidine with property of bitter taste was selected as a model
drug. Improvement in taste masking capability of cyclodextrin towards famotidine was evaluated by formulating a ternary complex
including hydrophilic polymer hydroxyl propyl methyl cellulose (HPMC 5 cps) as the third component. Phase solubility analysis
at 25 °C was carried out for both the binary systems (viz. drug–cyclodextrin and drug–polymer) and the ternary system (drug–cyclodextrin–polymer).
Ternary complex was prepared using solution method and was further characterized using XRD, DSC, FT-IR and microscopic studies.
In vitro dissolution study was carried out to see the effect of ternary complexation on drug release. Taste perception study was carried
out on human volunteers to evaluate the taste masking ability of ternary complexation. Results obtained from phase solubility
analysis showed that the combined use of polymer and cyclodextrin effectively increased the stability constant of the complex
[from 538 M−1 for binary system to 15,096 M−1 for ternary system]. Ternary system showed effective taste masking as compared to binary complex and at the same time showed
no limiting effect on the drug release (D.E15min = 90%). The effective taste masking was attributed to the enhanced complexation of famotidine in ternary system compared
to binary system and the same was confirmed from the characterization studies. In conclusion, the study confirmed that ternary
complexation can be utilized as an alternative approach for effective taste masking. 相似文献
946.
Molvi KI Sudarsanam V M Patel M Haque N 《Journal of enzyme inhibition and medicinal chemistry》2008,23(6):819-828
A new series of tetrasubstituted thiophene analogues (4a-4f, 5a-5f and 8a-8i) were designed incorporating the pharmacophoric features of COX-1 (as in fenamates), 5-LOX and the p38 MAP kinase inhibitors. The designed series was synthesized by nucleophilic addition of aryl/aroylisothiocyanate and enamine (2) yielding the addition product l-(alpha-Carbomethoxy-beta-aminothiocrotonoyl)-aryl/aroyl amines (3/7); which on reaction with substituted phenacyl bromides gave the targeted tetrasubstituted thiophene esters (4a-4f / 8a-8i). The tetrasubstituted thiophenes esters (4a-4f ) on hydrolysis with one equivalent of potassium hydroxide solution in methanol at room temperature gave corresponding acids (5a-5f ). All the targeted compounds were evaluated for their anti-inflammatory activity in carrageenin-induced rat hind paw oedema model at the doses of 10, 20 and 40 mg/kg body weight using standard drugs mefanamic acid and ibuprofen. The compounds (4c, 4e, 4f, 5f, 8a- 8i) which gave reasonable protection to the inflamed paw, eliciting good or moderate comparable anti-inflammatory activity were selected for investigating their analgesic activity using acetic acid induced writhing response test in albino mice at 10 mg/kg dose using standard drug ibuprofen and in order to arrive at possible mechanism of their anti-inflammatory activity, in vitro antioxidant nitric oxide radical scavenging assay at the concentrations of 5, 10, 15, 20, 25, 30 and 35 microg/mL were performed using standard drug ascorbic acid. 相似文献
947.
Hayden MR Karuparthi PR Habibi J Lastra G Patel K Wasekar C Manrique CM Ozerdem U Stas S Sowers JR 《Experimental biology and medicine (Maywood, N.J.)》2008,233(9):1109-1123
CONTEXT: The transgenic human islet amyloid polypeptide (HIP) rat model of type 2 diabetes mellitus (T2DM) parallels the functional and structural changes in human islets with T2DM. OBJECTIVE: The transmission electron microscope (TEM) was utilized to observe the ultrastructural changes in islet microcirculation. METHODS: Pancreatic tissue from male Sprague Dawley rats (2, 4, 8, 14 months) were used as controls (SDC) and compared to the 2-, 4-, 8- and 14-month-old HIP rat models. RESULTS: The 2-month-old HIP model demonstrated no islet or microcirculation remodeling changes when compared to the SDC models. The 4-month-old HIP model demonstrated significant pericapillary amyloid deposition and diminution of pericyte foot processes as compared to the SDC models. The 8-month-old model demonstrated extensive islet amyloid deposition associated with pericyte and beta-cell apoptosis when compared with SDC. The 14-month-old HIP model demonstrated a marked reduction of beta-cells and intra-islet capillaries with near complete replacement of islets by amyloidoses. Increased cellularity in the region of the islet exocrine interface was noted in the 4- to 14-month-old HIP models as compared to SDC. In contrast to intra-islet capillary rarefaction there was noticeable angiogenesis in the islet exocrine interface. Pericytes seemed to be closely associated with collagenosis, intra-islet adipogenesis and angiogenesis in the islet exocrine interface. CONCLUSION: The above novel findings regarding the microcirculation and pericytes could assist researchers and clinicians in a better morphological understanding of T2DM and lead to new strategies for prevention and treatment of T2DM. 相似文献
948.
949.
Price AL Patel NH 《Journal of experimental zoology. Part B. Molecular and developmental evolution》2008,310(1):24-40
The evolution of mesoderm was important for the development of complex body plans as well as key organ systems. Genetic and molecular studies in the fruitfly, Drosophila melanogaster, have provided the majority of information concerning mesoderm development in arthropods. In Drosophila, twist is necessary for the specification and correct morphogenesis of mesoderm and myocyte enhancing factor 2 (mef2) is involved downstream of twist to activate muscle differentiation. In Drosophila, mesoderm is defined by positional cues in the blastoderm embryo, while in another arthropod group, the amphipod crustaceans, cell lineage plays a greater role in defining the mesoderm. It is not known how different mechanistic strategies such as positional information vs. cell-lineage-dependent development affect the timing and use of gene networks. Here we describe the development of the mesoderm in a malacostracan crustacean, Parhyale hawaiensis, and characterize the expression of Parhyale twist and mef2 orthologues. In Parhyale, the mesoderm of the post-mandibular segments arises mainly through the asymmetric division of mesoteloblasts as the germband elongates. Ph-twist expression is seen in a subset of segmental mesoderm during germband development, but not during early cleavages when the specific mesodermal cell lineages first arise. ph-mef2 expression starts after the segmental mesoderm begins to proliferate and persists in developing musculature. While the association of these genes with mesoderm differentiation appears to be conserved across the animal kingdom, the timing of expression and relationship with different mechanisms of mesoderm development may give us greater insight into the ancestral use of these genes during mesoderm differentiation. 相似文献
950.
To begin to understand the interplay between autophagy and the hypersensitive response (HR), a type of programmed cell death (PCD) induced during plant innate immunity, we generated ATG6 antisense plants in the genetically tractable Arabidopsis thaliana system. AtATG6 antisense (AtATG6-AS) plants senesce early and are sensitive to nutrient starvation, suggestive of impairment of autophagic function in these plants. Additionally, these plants exhibited multiple developmental abnormalities, a phenomenon not observed in other AtATG mutants. AtATG6-AS plants produced fewer Monodansylcadaverine (MDC) and LysoTracker (LT) stained-autolysosomes in response to carbon and nitrogen starvation indicating that AtATG6 plays a role in the autophagic pathway in Arabidopsis. Interestingly, the level of AtATG6 mRNA in wild type Col-0 Arabidopsis plants is increased during the early phase of virulent and avirulent Pseudomonas syringae pv tomato (Pst) DC3000 infection suggesting that AtATG6 plays an important role during pathogen infection. In AtATG6-AS plants, HR-PCD induced upon infection with avirulent Pst DC3000 carrying the AvrRpm1 effector protein is not able to be contained at the infection site and spreads into uninfected tissue. Additionally, the disease-associated cell death induced by the infection of virulent Pst DC3000 bacteria is also partially misregulated in AtATG6-AS plants. Therefore, the AtATG6 antisense plants characterized here provide an excellent genetic model system to elucidate the molecular mechanisms by which autophagy regulates pathogen-induced cell death. 相似文献