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41.
Palaniappan Lakshmanan Ajay Sharma Sandeep Hemmadi John A Fairclough 《European journal of orthopaedic surgery & traumatology : orthopedie traumatologie》2004,14(4):249-251
Congenital dislocation of the knee (CDK) is not a common condition, and in most cases, reduction is performed by closed methods. We present two children with CDK who were refractory to conservative treatment. Surgical reduction was performed, and quadriceps lengthening was done by VY plasty in one and Z plasty in the other. At operation, it was difficult to identify the different muscle groups. Abnormal fibrous tissue was present in both the cases beneath the contracted quadriceps, which required complete excision. The child with Z plasty to lengthen the quadriceps had better range of motion in the knee than did the one with VY plasty. 相似文献
42.
Nitya Bakshi Ines Lukombo Helen Shnol Inna Belfer Lakshmanan Krishnamurti 《The journal of pain》2017,18(10):1216-1228
Sickle cell disease (SCD) is associated with episodes of severe vaso-occlusive pain beginning in infancy with a subset of patients with SCD transitioning to chronic pain. Response to experimental pain using quantitative sensory testing in these patients suggests altered pain processing. The objectives of this study were to characterize sensitivity to multiple modalities of experimental pain stimuli and to interrogate the relationship of psychological covariates, clinical pain burden, and pain-related outcomes to experimental pain sensitivity in children with SCD compared with healthy individuals of similar age and sex. Cross-sectional assessments of psychological characteristics were performed, and quantitative sensory testing methods were used to measure experimental pain sensitivity in children age 8 to 21 years. Anxiety, depressive symptoms, catastrophizing, and somatization were found to be associated with increased sensitivity to experimental pain stimuli. Increased frequency of painful episodes in SCD was associated with decreased sensitivity to heat pain and decreased mechanical temporal summation. These data suggest that careful consideration be given to psychological factors, age, sex, and clinical burden of pain when studying response to experimental pain in SCD.
Perspective
In this study of patients with SCD, a condition associated with recurrent acute or chronic pain, psychological factors such as depression, anxiety, and catastrophizing are associated with increased sensitivity to experimental pain stimuli. Further study is need to delineate the role of these factors in chronic SCD pain. 相似文献43.
Dr. Herand Abcarian M.D. Shanmugam Lakshmanan M.D. Don R. Read M.D. Peter Roccaforte Ph.D. 《Diseases of the colon and rectum》1982,25(6):525-528
Changes in anal sphincteric manometric pressures in response to rectal distention were measured in eight patients with chronic
anal fissures and were compared with the of ten controls. No statistically different resting pressures were noted between
the two groups. Overshoot phenomenon was more commonly seen in patients with fissure. There were no differences in the anal
sphincteric pressures after lateral internal sphincterotomy (LIS) or fissurectomy midline sphincterotomy (FMS). All fissures
healed postoperatively, irrespective of the surgical technique (LIS or FMS) or the pressure readings. It can be concluded
that the therapeutic effect of sphincterotomies might at least in part be due to anatomic widening of the anal canal rather
than to decreased resting pressures of the internal sphincter.
This study was supported by a grant from the American Society of Colon and Rectal Surgeons Research Foundation and was presented
as part of a symposium at the annual meeting of the American Society of Colon and Rectal Surgeons, Colorado Springs, Colorado,
June 7 to 11, 1981. 相似文献
44.
Aslanidi GV Rivers AE Ortiz L Govindasamy L Ling C Jayandharan GR Zolotukhin S Agbandje-McKenna M Srivastava A 《Vaccine》2012,30(26):3908-3917
Phosphorylation of surface-exposed tyrosine residues negatively impacts the transduction efficiency of recombinant AAV2 vectors. Pre-treatment of cells with specific cellular serine/threonine kinase inhibitors also significantly increased the transduction efficiency of AAV2 vectors. We reasoned that site-directed mutagenesis of surface-exposed serine residues might allow the vectors to evade phosphorylation and thus lead to higher transduction efficiency. Each of the 15 surface-exposed serine (S) residues was substituted with valine (V) residues, and the transduction efficiency of three of these mutants, S458V, S492V and S662V, was increased by up to ≈ 20-fold in different cell types. The S662V mutant was efficient in transducing human monocyte-derived dendritic cells (moDCs), a cell type not readily amenable to transduction by the conventional AAV vectors, and did not induce any phenotypic changes in these cells. Recombinant S662V-AAV2 vectors encoding a truncated human telomerase (hTERT) gene were generated and used to stimulate cytotoxic T cells (CTLs) against target cells. S662V-AAV2-hTERT vector-transduced DCs resulted in rapid, specific T-cell clone proliferation and generation of robust CTLs, which led to specific cell lysis of K562 cells. These studies suggest that high-efficiency transduction of moDCs by serine-modified AAV2 vectors is feasible, which supports the potential utility of these vectors for future human DCs vaccine studies. 相似文献
45.
Zhong L Li B Mah CS Govindasamy L Agbandje-McKenna M Cooper M Herzog RW Zolotukhin I Warrington KH Weigel-Van Aken KA Hobbs JA Zolotukhin S Muzyczka N Srivastava A 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(22):7827-7832
Recombinant adeno-associated virus 2 (AAV2) vectors are in use in several Phase I/II clinical trials, but relatively large vector doses are needed to achieve therapeutic benefits. Large vector doses also trigger an immune response as a significant fraction of the vectors fails to traffic efficiently to the nucleus and is targeted for degradation by the host cell proteasome machinery. We have reported that epidermal growth factor receptor protein tyrosine kinase (EGFR-PTK) signaling negatively affects transduction by AAV2 vectors by impairing nuclear transport of the vectors. We have also observed that EGFR-PTK can phosphorylate AAV2 capsids at tyrosine residues. Tyrosine-phosphorylated AAV2 vectors enter cells efficiently but fail to transduce effectively, in part because of ubiquitination of AAV capsids followed by proteasome-mediated degradation. We reasoned that mutations of the surface-exposed tyrosine residues might allow the vectors to evade phosphorylation and subsequent ubiquitination and, thus, prevent proteasome-mediated degradation. Here, we document that site-directed mutagenesis of surface-exposed tyrosine residues leads to production of vectors that transduce HeLa cells approximately 10-fold more efficiently in vitro and murine hepatocytes nearly 30-fold more efficiently in vivo at a log lower vector dose. Therapeutic levels of human Factor IX (F.IX) are also produced at an approximately 10-fold reduced vector dose. The increased transduction efficiency of tyrosine-mutant vectors is due to lack of capsid ubiquitination and improved intracellular trafficking to the nucleus. These studies have led to the development of AAV vectors that are capable of high-efficiency transduction at lower doses, which has important implications in their use in human gene therapy. 相似文献
46.
Carnitine (3-hydroxy-4N-trimethylammoniumbutanoate) is a naturally occurring quaternary amine that is ubiquitous in mammalian tissues (concentrations in the order of mM). Based on limited studies of approximately 40 years ago, carnitine was considered to be a peripheral antagonist of thyroid hormone (TH) action. These interesting observations have not been explored. To study the biologic basis of this effect, we tested the following possibilities in three TH-responsive cell lines: (1) inhibition of TH entry into cells; (2) inhibition of TH entry into the nucleus; (3) inhibition of TH interaction with the isolated nuclei; and (4) facilitated efflux of TH from cells. On a preliminary basis we had verified that these cell lines (human skin fibroblasts, human hepatoma cells HepG2, and mouse neuroblastoma cells NB 41A3) take up 14Ccarnitine; however, there was no 14Ccarnitine uptake into the nuclei. Concentrations of unlabeled carnitine as high as 100 mM did not affect (125I)T3 binding to isolated nuclei or exit of TH from cells, thus excluding possibilities numbered 3 and 4. At 10 mM camitine, (125I)T3 and (125I)T4 whole-cell uptake was inhibited by approximately 20% in fibroblasts and in HepG2, but by approximately 5% in NB 41A3 cells. Inhibition of T3 nuclear uptake was evaluated in HepG2 and NB 41A3 cells. At 10 mM carnitine, inhibition of T3 nuclear uptake was disproportionately higher, namely approximately 25% in neurons and 35% in hepatocytes. At 50 mM carnitine, there was a minimal additional decrease in whole-cell uptake of either hormone but a marked decrease in T3 nuclear uptake. The latter inhibition was approximately 60% in neurons and 70% in hepatocytes. We are aware of no inhibitor of TH uptake that has such a markedly different effect on the nuclear versus whole-cell uptake. Our data are consistent with carnitine being a peripheral antagonist of TH action, and they indicate a site of inhibition at or before the nuclear envelope. 相似文献
47.
The mechanism(s) responsible for the different biological potency of L- and D-T3 was investigated in rat L6E9 myoblasts. After incubation with intact cells at 37 C L-T3 cellular and nuclear uptakes were 91% and 70% higher than those of D-T3, respectively, but values for nuclear uptake as a fraction of cellular uptake were similar. The difference between the enantiomers was abolished at 4 C, and metabolic and endocytotic inhibitors reduced nuclear and extranuclear saturable uptake of L-T3 to a similar degree, but had little or no effect on D-T3 uptake. The affinity constants (Ka) for L- and D-T3 binding to isolated nuclei were similar, but the apparent nuclear Ka of L-T3 in intact cells was 5-fold greater than that of D-T3. The findings suggest that stereospecific transport, mainly active at the plasma membrane, occurs in rat skeletal muscle cells. This discriminative pathway of cell entry facilitates L-T3 uptake by an energy-dependent pathway not shared by D-T3 and may explain the greater potency of L-T3 than D-T3. 相似文献
48.
49.
Nivethitha Karthika Lakshmanan Praveen V Pavithran Nisha Bhavani Nithya Abraham Harish Kumar Vasantha Nair Usha Menon Arun S Menon Prem Narayanan Geetha Lakshmi 《Pediatric diabetes》2021,22(1):75-81
Monogenic forms of diabetes in children are frequently misclassified as either type 1 diabetes or young‐onset type 2 diabetes. There is a paucity of literature regarding pediatric monogenic diabetes in the Indian population. A retrospective analysis of case records of 37 children with monogenic diabetes who were diagnosed between 2008 and 2019 in a South Indian tertiary care center was performed. The write‐up describes the clinical, biochemical, and genetic characterization of these patients with the diagnoses of neonatal diabetes mellitus (15 patients), MODY (five patients), and various forms of syndromic diabetes (13 with Wolfram syndrome, two with H syndrome, one with mitochondrial diabetes, and one with thiamine responsive megaloblastic anemia). 相似文献
50.
Christopher J. Long Jason Van Batavia Amy B. Wisniewski Christopher E. Aston Laurence Baskin Earl Y. Cheng Yegappan Lakshmanan Theresa Meyer Bradley Kropp Blake Palmer Natalie J. Nokoff Alethea Paradis Brian VanderBrink Kristy J. Scott Reyes Elizabeth Yerkes Dix P. Poppas Larry L. Mullins Thomas F. Kolon 《Journal of pediatric urology》2021,17(3):379-386