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91.
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Yury M. Morozov Martin H. Dominguez Luis Varela Marya Shanabrough Marco Koch Tamas L. Horvath Pasko Rakic 《The European journal of neuroscience》2013,38(3):2341-2348
Anti‐cannabinoid type 1 receptor (CB1) polyclonal antibodies are widely used to detect the presence of CB1 in a variety of brain cells and their organelles, including neuronal mitochondria. Surprisingly, we found that anti‐CB1 sera, in parallel with CB1, also recognize the mitochondrial protein stomatin‐like protein 2. In addition, we show that the previously reported effect of synthetic cannabinoid WIN 55,212‐2 on mitochondrial complex III respiration is not detectable in purified mitochondrial preparations. Thus, our study indicates that a direct relationship between endocannabinoid signaling and mitochondrial functions in the cerebral cortex seems unlikely, and that caution should be taken interpreting findings obtained using anti‐CB1 antibodies. 相似文献
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Targeted deletion of histidine decarboxylase gene in mice increases bone formation and protects against ovariectomy-induced bone loss 总被引:7,自引:0,他引:7
Fitzpatrick LA Buzas E Gagne TJ Nagy A Horvath C Ferencz V Mester A Kari B Ruan M Falus A Barsony J 《Proceedings of the National Academy of Sciences of the United States of America》2003,100(10):6027-6032
Targeted disruption of the histidine decarboxylase gene (HDC(-/-)), the only histamine-synthesizing enzyme, led to a histamine-deficient mice characterized by undetectable tissue histamine levels, impaired gastric acid secretion, impaired passive cutaneous anaphylaxis, and decreased mast cell degranulation. We used this model to study the role of histamine in bone physiology. Compared with WT mice, HDC(-/-) mice receiving a histamine-free diet had increased bone mineral density, increased cortical bone thickness, higher rate of bone formation, and a marked decrease in osteoclasts. After ovariectomy, cortical and trabecular bone loss was reduced by 50% in HDC(-/-) mice compared with WT. Histamine deficiency protected the skeleton from osteoporosis directly, by inhibiting osteoclastogenesis, and indirectly, by increasing calcitriol synthesis. Quantitative RT-PCR showed elevated 25-hydroxyvitamin D-1alpha-hydroxylase and markedly decreased 25-hydroxyvitamin D-24-hydroxylase mRNA levels. Serum parameters confirming this indirect effect included elevated calcitriol, phosphorus, alkaline phosphatase, and receptor activator of NF-kappaB ligand concentrations, and suppressed parathyroid hormone concentrations in HDC(-/-) mice compared with WT mice. After ovariectomy, histamine-deficient mice were protected from bone loss by the combination of increased bone formation and reduced bone resorption. 相似文献
96.
A case of sparsely granulated growth hormone cell adenoma associated with lymphocytic hypophysitis. 总被引:1,自引:0,他引:1
Lymphocytic hypophysitis is in itself rare and usually occurs in the postpartum period or the last trimester of pregnancy. It has not been described in combination with a pituitary tumor. A twenty-two year old woman, who had never been pregnant, presented with a history of nine months amenorrhea and spontaneous galactorrhea. She was not taking any medication and had never used oral contraceptives. Physical examination was unremarkable except that whitish fluid could be expressed from both breasts. Her visual fields were normal. Her serum PRL levels was high at 105.7 micrograms/l and increased to 138.4 micrograms/l at 60 minutes in a triple bolus test. GH values were normal and there was no evidence of overproduction of other pituitary hormones. CT scan showed an intrasellar mass with suprasellar extension. A tumor was selectively removed transsphenoidally. Morphologic examination revealed a clinically silent sparsely granulated growth hormone cell adenoma with lymphocytic infiltration of the adjacent pituitary tissue. Postoperatively her menstrual periods resumed and she conceived despite a slightly elevated PRL level. Three months after an uneventful pregnancy and full term delivery her PRL level was 69.9 micrograms/l and increased to 102.2 micrograms/l at 60 min. Basal GH and cortisol levels were normal. She remains well without replacement fourteen months after delivery. This case is of interest because it is the first reported simultaneous occurrence of a pituitary adenoma and lymphocytic hypophysitis and also because the hypophysitis preceded her first pregnancy. 相似文献
97.
Hoeldtke RD Bryner KD Hobbs GR Horvath GG Riggs JE Christie I Ganser G Marcovina SM Lernmark A 《The Journal of clinical endocrinology and metabolism》2000,85(9):3297-3308
Autoimmune mechanisms have been implicated in the pathophysiology of diabetic neuropathy. We studied the association between glutamic acid decarboxylase (GAD65) and islet cell (IA-2) autoantibodies as well as autoantibodies to the autonomic nervous system and peripheral nerve function in recent onset type 1 diabetes. Thirty-seven patients (27 females and 10 males) enrolled 2-22 months after diagnosis. Humoral factors, glycemic control, and peripheral nerve function were measured annually for 3 yr. Patients with high GAD65Ab had worse glycemic control and higher insulin requirements. Patients with high GAD65Ab had slower motor nerve conduction velocities in the median, ulnar, and peroneal nerves (P < 0.025 for each nerve). The mean motor nerve conduction velocity Z scores at the time of the third evaluation was 0.341 +/- 0.25 for the low GAD65Ab patients and -0.600 +/- 0.25 for the high GAD65Ab patients (P < 0.01). Similar differences between the low and high GAD65Ab groups were observed for F wave latencies, thermal threshold detection, and cardiovascular autonomic function. The composite peripheral nerve function Z scores in the low GAD65Ab patients were 0.62 +/- 11, 0.71 +/- 0.19, and 0.21 +/- 0.14 at the first, second, and third evaluations, significantly different from those in the high GAD65Ab patients in whom they were -0.35 +/- 0.15, -0.46 +/- 0.18, and -0.42 +/- 0.16 (P < 0.001). In summary, GAD65Ab in patients with recent onset type 1 diabetes are associated with worse glycemic control and slightly worse peripheral nerve function. Although the latter remained within normal limits and none of the patients had clinical neuropathy, the GAD65Ab-related differences in composite peripheral nerve function were highly significant (P < 0.001) and could not be attributed to GAD65Ab-related differences in glycemic control. 相似文献
98.
Amino acid variations at a single residue in an autoimmune peptide profoundly affect its properties: T-cell activation, major histocompatibility complex binding, and ability to block experimental allergic encephalomyelitis. 下载免费PDF全文
V Kumar J L Urban S J Horvath L Hood 《Proceedings of the National Academy of Sciences of the United States of America》1990,87(4):1337-1341
Myelin basic protein (MBP) or helper T cells reactive against MBP induce an autoimmune disease, experimental allergic encephalomyelitis, in B10.PL and PL/J inbred mice. In both strains, virtually the entire repertoire of MBP-specific T cells recognize an N-terminal peptide fragment in the context of the I-Au molecule encoded by the major histocompatibility complex (MHC) and utilize a very limited set of T-cell receptor genes. To delineate the nature of the trimolecular complex, consisting of the T-cell receptor, MBP-peptide fragment, and MHC molecule (I-Au), we have synthesized 13 variants of the 9-mer N-terminal immunodominant peptide differing at residue 4 and studied their immune recognition in vitro and in vivo. These substitutions have a striking range of effects on T-cell activation, ability to bind to the MHC molecule, and initiation of immune responses in vivo. An understanding of the autoimmune peptide/MHC/T-cell receptor interactions allowed us to design variant 9-mer peptides that have high affinity for an MHC molecule and are effective in blocking experimental allergic encephalomyelitis, possibly through two distinct mechanisms, peripheral T-cell tolerance and the inhibition of binding of the encephalitogenic peptide to the MHC molecules. 相似文献
99.
Droppa M Terry N Horvath G 《Proceedings of the National Academy of Sciences of the United States of America》1984,81(8):2369-2373
The role of copper (Cu) in photosynthetic electron transport was explored by using Cu deficiency in sugar beet as an experimental approach. Copper influenced electron transport at two sites in addition to plastocyanin. Under mild deficiency (0.84 nmol of Cu per cm2 of leaf area), electron transport between the two photosystems (PS) is inhibited but not electron transport within PS I or PS II measured separately. The chlorophyll/plastoquinone ratio was normal in Cu-deficient plants. However, the breakpoint in the Arrhenius plot of electron transport was shifted towards a higher temperature. It is concluded that Cu is necessary to maintain the appropriate membrane fluidity to ensure the mobility of plastoquinone molecules to transfer electrons between the two photosystems. Under severe deficiency (0.22 nmol of Cu per cm2 of leaf area) both PS II and PS I electron transports were inhibited and to the same extent. PS II electron transport activity could not be restored by adding artificial electron donors. Polypeptides with Mrs of 28,000 and 13,500 were missing in Cu-deficient chloroplast membranes. In PS II particles prepared from normal chloroplasts of spinach, 2 atoms of Cu per reaction center are present. We conclude that Cu influences PS II electron transport either directly, by participation in electron transfer as a constituent of an electron carrier, or indirectly, via the polypeptide composition of the membrane in the PS II complex. 相似文献
100.