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951.
Non-organ-specific autoantibodies in renal transplant recipients: relation to BK virus infection 总被引:1,自引:0,他引:1
Costa C Touscoz GA Bergallo M Sidoti F Terlizzi ME Astegiano S Merlino C Segoloni GP Cavallo R 《The new microbiologica》2008,31(2):175-180
Polyomavirus BK reactivation is common in renal transplant recipients and may cause nephropathy with significant graft dysfunction. The induction of anti-double stranded DNA (anti-dsDNA) antibodies by BKV has been described in experimental animals and during primary infection, and has been implicated in the pathogenesis of systemic lupus erythematosus. This study evaluated the occurrence of anti-dsDNA antibodies and non-organ-specific autoantibodies (NOSA) by indirect immunofluorescence before transplantation and at 3 and 6 months post-transplantation in 90 renal transplant recipients and the association with BKV reactivation, demographic and clinical features. Moreover, the relation to HCMV infection, as detected by pp65-antigenemia, was also evaluated. Post-transplantation NOSAs were present in 23/90 (25.6%) and anti-dsDNA antibodies in 17/90 (18.9%). BK viremia was detected in at least one serum sample in 22 patients: 9 anti-dsDNA antibody-positive vs 13 negative (p<0.01). No significant correlation between the occurrence of NOSAs and anti-dsDNA antibodies and demographic and clinical features was found. No significant association with pp65-antigenemia-positivity was found, although antigenemia was positive in 6/23 NOSA-positive patients (26.1%). Although a relation seems to exist between BKV and the occurrence of anti-dsDNA antibodies in renal transplant patients, the lack of correlation with other epidemiological and clinical features does not allow any conclusion. The role of autoimmune response in this context and the relation with other patient-related factors and infectious agents should be further investigated. 相似文献
952.
953.
Robertsonian translocations, also called centric fusions, represent the most frequent chromosome anomalies in cattle, and rob(1;29) is the most widespread. However, centric fusions involving other chromosomes have been discovered in different cattle breeds. Here we report the appearance of a new case of rob(14;17) in an Italian cattle breed more than ten years after the first and only case had been observed, and we demonstrate the independent origin of this anomaly from the previous case. 相似文献
954.
Tyzzer discovered the genus Cryptosporidium a century ago, and for almost 70 years cryptosporidiosis was regarded as an infrequent and insignificant infection that occurred in the intestines of vertebrates and caused little or no disease. Its association with gastrointestinal illness in humans and animals was recognized only in the early 1980s. Over the next 25 years, information was generated on the disease's epidemiology, biology, cultivation, taxonomy and development of molecular tools. Milestones include: (i) recognition in 1980 of cryptosporidiosis as an acute enteric disease; (ii) its emergence as a chronic opportunistic infection that complicates AIDS; (iii) acknowledgement of impact on the water industry once it was shown to be waterborne; and (iv) study of Cryptosporidium genomics. 相似文献
955.
Background
Elevations of serum prolactin (PRL) are associated with an increased risk for breast cancer. PRL signaling through its prolactin receptor (PRLr) involves the Jak2/Stat5 pathway. Luciferase-based reporter assays have been widely used to evaluate the activity of this pathway. However, the existing reporters are often not sensitive enough to monitor the effect of PRL in this pathway. 相似文献956.
Diego Calzolari Stefania Bruschi Laurence Coquin Jennifer Schofield Jacob D. Feala John C. Reed Andrew D. McCulloch Giovanni Paternostro 《PLoS computational biology》2008,4(12)
Combination therapies are often needed for effective clinical outcomes in the management of complex diseases, but presently they are generally based on empirical clinical experience. Here we suggest a novel application of search algorithms—originally developed for digital communication—modified to optimize combinations of therapeutic interventions. In biological experiments measuring the restoration of the decline with age in heart function and exercise capacity in Drosophila melanogaster, we found that search algorithms correctly identified optimal combinations of four drugs using only one-third of the tests performed in a fully factorial search. In experiments identifying combinations of three doses of up to six drugs for selective killing of human cancer cells, search algorithms resulted in a highly significant enrichment of selective combinations compared with random searches. In simulations using a network model of cell death, we found that the search algorithms identified the optimal combinations of 6–9 interventions in 80–90% of tests, compared with 15–30% for an equivalent random search. These findings suggest that modified search algorithms from information theory have the potential to enhance the discovery of novel therapeutic drug combinations. This report also helps to frame a biomedical problem that will benefit from an interdisciplinary effort and suggests a general strategy for its solution. 相似文献
957.
Radi M Crespan E Botta G Falchi F Maga G Manetti F Corradi V Mancini M Santucci MA Schenone S Botta M 《Bioorganic & medicinal chemistry letters》2008,18(3):1207-1211
A series of substituted benzoylamino-2-[(4-benzyl)thio]-1,3,4-thiadiazoles has been discovered as potent Abl tyrosine kinase inhibitors. Molecular docking simulations on the Abl tyrosine kinase were conducted in order to rationalize the SAR of the synthesized inhibitors. The most active compound identified from the enzymatic screening (6a) showed interesting inhibitory activity on Imatinib-sensitive murine myeloid 3B clone and Bcr-Abl-independent Imatinib-resistant leukemia cells. Surprisingly, 6a was also proved to act as differentiating inducers in human promyelocytic leukemia cells (HL-60). 相似文献
958.
Guerrini G Ciciani G Cambi G Bruni F Selleri S Melani F Montali M Martini C Ghelardini C Norcini M Costanzo A 《Bioorganic & medicinal chemistry》2008,16(8):4471-4489
The synthesis and binding studies of a series of 3-acylpyrazolo[5,1-c][1,2,4]benzotriazine 5-oxides 8-substituted are reported. High-affinity ligands at benzodiazepine site on GABA(A) receptor complex (GABA(A)/BzR complex) were obtained when the 3-aroyl substituent is represented by a five-member heteroaroyl ring (furoyl-, thenoyl-, and pyrroyl-). Moreover the type of heteroaroyl ring at position 3 influences the feature of the substituent at position 8 to obtain high-affinity ligands: a 'hydrogen-bond acceptor ring' at position 3 is synergic with an electron donor substituent at position 8, while a 'hydrogen-bond donor ring' is synergic with a withdrawing substituent. Compounds 8a, 9b, and 11 were deeply studied in vivo for their pharmacological effects considering six potential benzodiazepine actions: motor coordination, anticonvulsant action, spontaneous motor activity and explorative activity, anxiolytic-like effects, mouse learning and memory modulation, and ethanol-potentiating action. To rationalize and qualitatively interpret the GABA(A)/Bz binding affinities of compounds 8a and 11, a dynamic molecular modeling study has been performed, with the aim of assessing the preferred geometry of protein-ligand complex. 相似文献
959.
Tabrizi MA Baraldi PG Preti D Romagnoli R Saponaro G Baraldi S Moorman AR Zaid AN Varani K Borea PA 《Bioorganic & medicinal chemistry》2008,16(5):2419-2430
A new series of 1,3-dipropyl-8-(1-phenylacetamide-1H-pyrazol-3-yl)-xanthine derivatives has been identified as potent A(2B) adenosine receptor antagonists. The products have been evaluated for their binding affinities for the human A(2B), A(1), A(2A), and A(3) adenosine receptors. N-(4-chloro-phenyl)-2-[3-(2,6-dioxo-1,3-dipropyl-2,3,6,7-tetrahydro-1H-purin-8-yl)-5-methyl-pyrazol-1-yl] (11c) showed a high affinity for the human A(2B) adenosine receptor K(i)=7nM and good selectivity (A(1), A(2A), A(3)/A(2B)>140). Synthesis and SAR of this novel class of compounds is presented herein. 相似文献
960.
Giovanni Minervini Giuseppe Evangelista Fabio Polticelli Monika Piwowar Marek Kochanczyk Lukasz Flis Maciej Malawski Tomasz Szepieniec Zdzisaw Winiowski Ewa Matczyska Katarzyna Prymula Irena Roterman 《Bioinformation》2008,3(4):177-179
The number of natural proteins although large is significantly smaller than the theoretical number of proteins that can be obtained combining the 20 natural amino acids, the so-called “never born proteins” (NBPs). The study of the structure and properties of these proteins allows to investigate the sources of the natural proteins being of unique characteristics or special properties. However the structural study of NPBs can also been intended as an ideal test for evaluating the efficiency of software packages for the ab initio protein structure prediction. In this research, 10.000 three-dimensional structures of proteins of completely random sequence generated according to ROSETTA and FOD model were compared. The results show the limits of these software packages, but at the same time indicate that in many cases there is a significant agreement between the prediction obtained. 相似文献