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31.
32.
33.
Specific cytotoxic T lymphocytes in gene therapy 总被引:1,自引:0,他引:1
U. Altenschmidt Dirk Moritz B. Groner 《Journal of molecular medicine (Berlin, Germany)》1997,75(4):259-266
Cytotoxic T lymphocytes possess the capacity to lyse target cells which express antigens on their surface recognized by the
T cell receptor. These cells are crucial in the body’s defense against foreign antigens. It has long been a goal of tumor
biology to utilize T cells, specialized in the elimination of unwanted cells, for the treatment of cancer. The killing activity
of T lymphocytes is restricted to specific antigen-presenting cells. For this reason the use of cytotoxic T cells in the elimination
of cancer cells is limited to cancer cells which present neoantigens on their surface. To circumvent this limitation we describe
a procedure in which the ζ component of the T cell receptor is genetically manipulated and equipped with an extracellular
recognition domain. Introduction of a chimeric gene, consisting of the ζ chain of the T cell receptor and a single-chain antibody
domain, into cytotoxic T lymphocytes results in T cells with a predetermined recognition specificity for particular tumor
cells. The MHC restriction of target cell recognition can be avoided and tumor cells recognized by the single chain antibody
domain can be recognized and lysed. Retroviral-mediated gene transduction was used to introduce chimeric ζ chain constructs
into primary T cells of mice. The cocultivation of retrovirus producing helper cells with in vitro activated T lymphocytes
led to a high gene transduction efficiency into primary T cells. These primary T cells assumed a predetermined specificity
for target cell recognition and lysis. The production and provision of tumor cell specific T lymphocytes might not be sufficient
to eradicate large tumors in vivo. Using a Schwannoma cell line, we showed that transplanted tumors secrete transforming growth
factor β and thereby stifle the action of lymphocytes. We suggest that a coordinated strategy including the suppression of
tumor cells specific antilymphocyte action and the provision of tumor cell specific T cells might be required to successfully
eliminate tumor cells in vivo.
Received: 13 September 1996 / Accepted: 30 October 1996 相似文献
34.
Katrin Banach Moritz Bünemann Jörg Hüser Lutz Pott 《Pflügers Archiv : European journal of physiology》1993,423(3-4):245-250
L-type Ca2+ current (I
Ca) was measured in cultured atrial myocytes from hearts of adult guinea-pigs using whole-cell voltage clamp. Potentiation of I
Ca induced by -adrenergic stimulation (isoprenaline 2· 10–7 M) could be completely antagonized by diluted sera (1100 v/v). Half-maximal inhibition of -receptorstimulated I
Ca occurred at about 11000. Basal I
Ca was not affected by serum. Atropine in a concentration (10–6M) that completely antagonized the anti-adrenergic effect of acetylcholine (ACh, 2·10–6 M) did not interfere with the effect of serum. In cells dialysed with cyclic adenosine monophosphate (cAMP)-containing (10–4 M) pipette solution, potentiated I
Ca was insensitive to both ACh and serum. Preincubation of the myocytes with pertussis toxin almost completely abolished the anti-adrenergic effects of both ACh and serum. The potency of serum was not reduced by dialysis. It is concluded that serum contains a factor which, like ACh, inhibits -receptor-stimulated adenylyl cyclase via Giprotein.A preliminary report of this work has appeared in abstract form [11] 相似文献
35.
Cholecystokinin-decreased food intake in rhesus monkeys 总被引:1,自引:0,他引:1
36.
Fugger EF; Black SH; Keyvanfar K; Schulman JD 《Human reproduction (Oxford, England)》1998,13(9):2367-2370
The world's first deliveries of normal babies after use of flow cytometric
separated human sperm cells (MicroSort) for preconception gender selection
are reported. Offspring were of the desired female gender in 92.9% of the
pregnancies. Most of these pregnancies and births were achieved after
simple intrauterine insemination.
相似文献
37.
Horne G; Jamaludin A; Critchlow JD; Falconer DA; Newman MC; Oghoetuoma J; Pease EH; Lieberman BA 《Human reproduction (Oxford, England)》1998,13(11):3045-3048
Insemination with donor spermatozoa is an integral part of infertility
treatment. For the last 3 years in our unit, intrauterine insemination with
donor spermatozoa (IUID) has been used in preference to vaginal
insemination. In this retrospective study, patients were offered an initial
course of five single intrauterine inseminations with cryopreserved donor
spermatozoa and treatment was then reviewed. A total of 389 patients
received 1465 inseminations. In all, 1119 cycles were monitored using
luteinizing hormone serum analyses and 346 cycles using the urine home test
kits. The clinical pregnancy rate per insemination for the cycles monitored
by the serum assay was 18.0% (202/1119) compared with the urine cycles
(13.7%, 46/346) (P <05). The pregnancy loss rate was not significantly
different (14.4%, 29/202 and 21.7%, 10/46) (serum and urine cycles
respectively). The viable clinical pregnancy rate was significantly higher
(P <03) for the serum cycles than for the cycles using the urinary
monitoring (15.5%, 173/1119 and 10.4%, 36/346 respectively). The cycles
monitored by serum assay had a significantly higher cumulative viable
clinical pregnancy rate (P <0001) of 70.2% after nine inseminations
compared with the urine monitored cycles of 54.8%. The majority of patients
opted for the serum cycles, with a minority self-selecting the urine cycles
mainly for travelling convenience. The explanation for the significant
differences between the viable clinical pregnancy rates per insemination
and the cumulative viable clinical pregnancy rates may be due to the
sensitivity of the urine home test kit or the patients' interpretation of
the result.
相似文献
38.
Recessively inherited L-DOPA-responsive parkinsonism in infancy caused by a point mutation (L205P) in the tyrosine hydroxylase gene 总被引:4,自引:0,他引:4
39.
Moritz S Andresen B Domin F Martin T Probsthein E Kretschmer G Krausz M Naber D Spitzer M 《Psychological medicine》1999,29(1):161-170
BACKGROUND: Previous studies on semantic priming have suggested that schizophrenic patients with language disturbances demonstrate enhanced semantic and indirect semantic priming effects relative to controls. However, the interpretation of semantic priming studies in schizophrenic patients is obscured by methological problems and several artefacts (such as length of illness). We, therefore, used a psychometric high-risk approach to test whether healthy subjects reporting language disturbances resembling those of schizophrenics (as measured by the Frankfurt Complaint Questionnaire subscale 'language') display increased priming effects. In addition, the Schizotypal Personality Questionnaire was used to cover symptoms of schizotypal personality. Enhanced priming was expected to occur under conditions favouring automatic processes. METHODS: One hundred and sixty healthy subjects performed a lexical decision semantic priming task containing two different stimulus onset asynchronicities (200 ms and 700 ms) with two experimental conditions (semantic priming and indirect semantic priming) each. RESULTS: Analyses of variance revealed that the Frankfurt Complaint Questionnaire-' language' high scorers significantly differed from low scorers in three of the four priming conditions indicating increased automatic spreading activation. No significant results were obtained for the Schizotypal Personality Questionnaire total and subscales scores. CONCLUSIONS: In line with Maher and Spitzer it is suggested that increased automatic spreading activation underlies schizophrenia-typical language disturbances which in our study cannot be attributed to confounding variables such as different reaction time baselines, medication or length of illness. Finally, results confirm that the psychometric high-risk approach is an important tool for investigating issues relevant to schizophrenia. 相似文献
40.
Beta2-adrenergic receptors mediate the differential effects of catecholamines on cytokine production of PBMC. 总被引:1,自引:0,他引:1
M Wahle R P Neumann F Moritz A Krause F Buttgereit C G O Baerwald 《Journal of interferon & cytokine research》2005,25(7):384-394
We determined characteristics of beta2-adrenergic receptors (beta2R) on peripheral blood mononuclear cells (PBMC) and cytokine production after mitogenic stimulation and coincubation with catecholamines. PBMCs were stimulated with interleukin-2 (IL-2), tetanus toxoid (TT), anti-CD3 antibody, or phytohemagglutinin (PHA). The cytokines interferon-gamma (IFN-gamma), IL-4, and IL-6 were determined by ELISA following coincubation with high-dose (10(-5) M) and low-dose (10(-9) M) epinephrine (EPI) and norepinephrine (NE). Intracellular IFN-gamma and IL-4 were studied by FACS analysis. The beta2R density was investigated using a radioligand binding assay. The stimuli induced various cytokine profiles in PBMCs. Synthesis of IFN-gamma was induced by all mitogens and could be suppressed by catecholamines (26%-85% reduction). In PHA-stimulated PBMCs, IL-4 synthesis was decreased by high-dose catecholamines (24%-28% reduction). Adding a beta-blocking agent attenuated most catecholamine effects. A highly significant negative correlation between the density of beta2R with IFN-gamma and IL-6 levels of PHA-activated PBMCs (r = -0.88 to -0.96, p < 0.01-< 0.001) was observed. The results indicate that the density of beta2R on PBMC plays a role in mediating the differential catecholamine effects on cytokine production of PBMC. Furthermore, changes in cytokine expression induced by catecholamines favor Th2 responses. 相似文献