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51.
Siddharth K. Prakash Soniely Lugo‐Ruiz Michelle Rivera‐Dávila Nunilo Rubio Jr. Avni N. Shah Rebecca C. Knickmeyer Cindy Scurlock Melissa Crenshaw Shanlee M. Davis Gary A. Lorigan Aaron T. Dorfman Karen Rubin Cheryl Maslen Vaneeta Bamba Paul Kruszka Michael Silberbach Scientific Advisory Board of the TSRR 《American journal of medical genetics. Part C, Seminars in medical genetics》2019,181(1):7-12
To address knowledge gaps about Turner syndrome (TS) associated disease mechanisms, the Turner Syndrome Society of the United States created the Turner Syndrome Research Registry (TSRR), a patient‐powered registry for girls and women with TS. More than 600 participants, parents or guardians completed a 33‐item foundational survey that included questions about demographics, medical conditions, psychological conditions, sexuality, hormonal therapy, patient and provider knowledge about TS, and patient satisfaction. The TSRR platform is engineered to allow individuals living with rare conditions and investigators to work side‐by‐side. The purpose of this article is to introduce the concept, architecture, and currently available content of the TSRR, in anticipation of inviting proposals to utilize registry resources. 相似文献
52.
The possible immunomodulatory influence of thymosin on lymphocytes from patients with active systemic lupus erythematosus (SLE) has been evaluated. Such patients have decreased numbers of T-suppressor (Tγ) cells and normal numbers of T-helper (Tμ) cells, resulting in an abnormally low Tγ/Tμ ratio. In vitro incubation of lymphocytes from active SLE patients with thymosin resulted in a normalization of the Tγ/Tμ ratio. This occurred because of a decrease in Ty cells rather than an increase in Tγ cells. The normalization of Tγ/Tμ ratios in vitro in the presence of thymosin is compatible with possible in vivo immunomodulatory effects of these peptides. 相似文献
53.
The productive activation of CD4(+) T lymphocytes, leading to proliferation and cytokine secretion, requires precise temporal regulation of intracellular cyclic AMP concentrations. The major effector molecule activated by cyclic AMP in mammalian cells is the cyclic AMP-dependent protein kinase A (PKA). The type I PKA isozyme mediates the inhibitory effects of cyclic AMP on T-cell activation. Using laser scanning confocal microscopy, we demonstrated that the regulation of PKA type I activity involves spatial redistribution of PKA type I molecules following T-cell receptor (TCR) stimulation. In resting T cells, PKA type I was located in membrane proximal regions and distributed equally across the cell. Shortly after antigen engagement, T cells and antigen-presenting cells formed an area of intense contact, known as the immunological synapse. TCR concentrated at the synapse, whereas PKA type I molecules redistributed to the opposite cell pole within 10 min after T-cell stimulation. Type I PKA redistribution was solely dependent on TCR signalling, because we observed the same temporal and spatial distribution after antibody-mediated cross-linking of the TCR-associated CD3 complex. Segregation of TCR and PKA type I molecules was maintained for at least 20 min. Thirty minutes after stimulation, PKA type I partially colocalized with the TCR. After 60 min, PKA type I distribution again approached the resting state. Considering that initial TCR signals lead to increases in intracellular cyclic AMP, PKA type I molecules may be targeted towards localized cyclic AMP accumulations or transported away from these areas, depending on the requirements of the cellular response. 相似文献
54.
Loss of Fhit expression in testicular germ cell tumors and intratubular germ cell neoplasia. 总被引:2,自引:0,他引:2
The FHIT gene, located at human chromosome 3p14.2, is frequently deleted in a number of human cancers, and interstitial deletions at this site were recently described in a significant proportion (41%) of testicular germ cell tumors. We studied the expression of Fhit protein in the progression and differentiation of testicular germ cell tumors to further elucidate its role in this type of malignancy. Forty-five patients with testicular germ cell tumors and intratubular germ cell neoplasia (identified in 42/45 cases) were included in the study. Immunohistochemical staining with polyclonal rabbit IgG antibody to Fhit (ZR44, Zymed Laboratories) on formalin-fixed, paraffin-embedded tissues was used. Fhit was constitutively expressed in germ cells, Sertoli cells, and Leydig cells. All 42 cases of intratubular germ cell neoplasia revealed no expression of this protein. No expression of Fhit was observed in any case of pure seminoma or in the seminomatous component of mixed germ cell tumors. Unexpectedly, Fhit expression was frequently (16/18) observed in the glandular tissue of mature teratomatous component of mixed germ cell tumors, despite the absence of Fhit in the intratubular germ cell neoplasia, the presumed precursor lesion. The loss of Fhit expression is a consistent characteristic of intratubular germ cell neoplasia, which suggests a potential role in a maturation/differentiation defect early in the development of testicular germ cell tumors. Likewise, the lack of expression in seminomas is supportive of this view. However, re-expression of Fhit in well-differentiated glandular epithelium of teratomatous component of mixed germ cell tumors suggests that there is no loss of FHIT gene in this subset of neoplasia but rather that Fhit protein expression is differently regulated through the phases of germ cell tumor progression. 相似文献
55.
Yuan B. Peng Qing Lin W. D. Willis 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1997,114(3):561-570
The effects of a protein kinase C (PKC) activator, 12-O-tetradecanoylphorbol-13-acetate (TPA), on the activity and periaqueductal gray (PAG)-induced inhibition of rat dorsal horn
neurons of the lumbar spinal cord were tested. A microdialysis fiber was placed through the dorsal horn for the purpose of
local application of pharmacological agents. Extracellular single-unit recordings from dorsal horn neurons were made near
the microdialysis fiber. TPA was tested on nociceptive dorsal horn cells. There was a significant increase in the background
activity and responses to ”brush”, with no changes in responses to pressure and pinch stimuli. TPA also significantly blocked
the PAG-induced inhibition of responses to brush, press, and pinch. These effects were eliminated by coadministration of the
PKC inhibitor NPC-15437. The solvent, which contained dimethyl sulfoxide, was also tested for its effect on the responses
to peripheral mechanical stimuli and PAG-induced inhibition of the dorsal horn neurons. There were no significant changes.
This experiment suggests that activation of the PKC second messenger system might increase the activity of dorsal horn neurons
and their responses to peripheral stimuli; in addition, the phorbol ester attenuated the PAG-induced descending inhibition
of the dorsal horn neuron activity.
Received: 15 May 1996 / Accepted: 14 November 1996 相似文献
56.
We have previously shown that natural killer (NK) cell activity against K562 tumor cells is severely depressed in thermal injury patients. In this study we have investigated whether the low NK cell activity present in peripheral blood lymphocytes (PBL) from thermal injury patients could be enhanced byin vitro culture with interleukin 2 (IL2) and whether PBL obtained from these patients could generate lymphokine-activated killer (LAK) cell activity against NK insensitive tumor targets. NK cell activity in PBL obtained from 12 different patients was greatly enhanced against K562 tumor cells afterin vitro culture with IL2 for 3 days. In contrast, PBL obtained from these patients and incubated with IL2 had little to no cytotoxic activity when measured against a number of NK-insensitive tumor targets. The failure of PBL obtained from thermal injury patients to generate LAK cell activity was observed regardless of the culture time or the amount of IL2 added to the cultures. PBL from thermal injury patients demonstrated reduced proliferative responses to IL2 and, more importantly, contained suppressor cells which could inhibit the generation of LAK cell activity of normal PBL obtained from control individuals. These results clearly show that in some thermal injury patients NK cell activity can be enhanced by IL2 but these patients are defective in their ability to generate LAK cell activity. 相似文献
57.
Electron micrographs of random sections through 133 astrocytes taken from the anterior and posterior sigmoid gyri of adult cats were used to estimate average astrocyte cell volume. Average soma volume was derived by two methods: (1) assuming that each approximated the shape of a prolate spheroid, a value of 2.2 ± 0.1 × 10?13l. was calculated by substituting measurements of major (mean 10.4 ± 0.2 μm) and minor (mean 6.2 ± 0.1 μm) cell axes into the formula for volume; (2) applying Weibel's point-counting method of morphometry, a value of 1.9 ± 0.09 × 10?13l. was obtained based on ratios of volume density and nuclear volume, calculated from measurements of nuclear axes. Because of the use of random sections through the cells sampled, the axial measurements on which both methods depend represent possible underestimations by as much as 21%; the resulting average value for soma volume might be as much as 3.2 × 10?13l. Astrocyte somata from the deepest layer of the cortex had a significantly larger average volume than those from more superficial layers (P < 0.05). Average total cell volume (soma plus processes), estimated by calculating the volume of the tissue sample that was occupied by astrocytes and dividing that value by the number of astrocytes in the sample, amounted to 5.7 × 10?13l. Point-counting morphometry revealed that 15.5% of the cortex consists of astrocytic cytoplasm. Average total cell surface area, estimated from intercepts of grid lines with cell membrane profiles of astrocytes within the sample, was 1.9 × 10?5 cm2; average surface area of astrocyte somata, based on axial measurements, amounted to 2.5 × 10?6 cm2 or 13% of the surface area of the whole cell.Only 18 gap junctions were identified in the random sections through 133 astrocytes; these and other considerations bearing on the possible relationship of the data presented to electrical measurements in living astrocytes are discussed. 相似文献
58.
Barbara H. Bowman Lillian H. Lockhart Victoria L. Herzberg Don R. Barnett Donald Armstrong John Kramer 《Clinical genetics》1973,4(6):461-463
The presence of a ciliary inhibitor in media of cultured amniotic cells obtained from a fetus heterozygous for cystic fibrosis has been observed by the oyster gill cilia assay. The chromatographic fraction containing the inhibitor corresponded to eluted fractions chromatographed from cystic fibrosis fibroblast media and serum. An analogous chromatographic fraction from media of cultured amniotic cells from two proportedly normal fetuses did not inhibit cilia. The chromatographic fraction from media of cultured amniotic cells of a fetus at high risk for cystic fibrosis did not inhibit ciliary activity. Serum was collected from this baby seven weeks after birth and also did not inhibit ciliary action, indicating a homozygous normal genotype. These observations may lead to the development of an antenatal test for cystic fibrosis. 相似文献
59.
When human peripheral blood lymphocytes (PBL) are cultured with either concanavalin A (Con A)-treated or control autologous T lymphocytes, the mitogenic responses of the PBL co-cultured with Con A-treated cells are much lower. We have investigated the cell surface receptor changes during culture of T cells with and without mitogen in an attempt to explain this differential regulatory phenomenon. We present data here which show that human T cells cultured in complete medium alone gain helper cells with time. Con A-treated T cells are known to lose helper cells during culture. Erythrocyte rosette-purified T cells were cultured with or without Con A for 84 h and the numbers of cells with receptors for the Fc regions of either IgM (T mu) or IgG (T gamma) were enumerated daily. T mu cells have been associated with helper activity while T gamma cells have predominantly suppressor activity. Treatment with 10 micrograms/ml of Con A decreased T mu by approximately 50%. Untreated cells, however, showed significant increases in T mu (44 +/- 30.5% in twelve individuals). The great variance in T mu increases is due to the fact that individuals having higher initial T mu values showed smaller increases. These changes probably represent the gain or loss of receptors because total cell numbers did not change. There was no significant change in the number of T gamma cells in either control or Con A-treated cultures during the same 84 h period. In co-culture experiments in which the responses of fresh autologous PBL were determined, 60-h control T-cell cultures enhanced the mitogen responses of the fresh cells.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
60.
Pre-eclampsia, one of the most significant health problems inhuman pregnancy, complicates 6-7% of all gestations and is theleading cause of fetal growth retardation, infant morbidityand mortality, premature birth and maternal death. Recent researchimplicates free radicals in the pathophysiology of pre-eclampsia.This review covers the biochemistry of nitric oxide (NO) andpossible interactions with other free radicals. Studies in therat show that pregnancy is associated with enhanced productionand responsiveness to NO in both reproductive tissues and bloodvessels. Rats infused with NG-nitro-L-arginine methyl ester(L-NAME, a NO synthase inhibitor) have been used as an animalmodel of pre-eclampsia, and the effects of steroid hormoneson blood pressure in this model have been tested. Results suggestthat pre-eclampsia may be a state of NO deficiency. However,in humans there seem to be contradictions regarding the involvementof NO in maternal adaptation to pregnancy. It is suggested thatNO may be one of several systems that act in concert to maintaina symbiotic relationship between mother and fetus. However,the input of each system may be genetically determined. 相似文献