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101.
102.
Talpaz M; Kantarjian HM; McCredie KB; Keating MJ; Trujillo J; Gutterman J 《Blood》1987,69(5):1280-1288
Fifty-one patients with previously untreated or minimally treated chronic myelogenous leukemia in chronic phase received human alpha interferon 3 to 9 X 10(6) units intramuscularly (IM) daily until complete hematologic remission, then at doses ranging from 3 X 10(6) units every other day to 9 X 10(6) units daily. Forty-one (80%) patients achieved a hematologic response, 36 (71%) of them attaining a complete hematologic remission with normal peripheral WBC and differential counts. Responding patients showed continuous but slow normalization of several other blood and marrow parameters including platelet counts, serum lactic dehydrogenase and B12 levels, and marrow cellularity and maturation index. Suppression of the Philadelphia chromosome on serial cytogenetic studies of marrow metaphases was documented in 20 of the 36 patients who achieved complete hematologic remission (56%; 39% of total group), eight of whom (22%) had a decrease of the Philadelphia chromosome-positive metaphases to less than 35%. These changes were persistent for 6 months or longer in 18 patients, seven of whom had continuous suppression of the Philadelphia chromosome to less than 90% for a median of 30+ months (range 21+ to 39+ months). After a median follow-up period of 37 months, 25 patients remain in continued disease control with interferon therapy. The projected 3-year survival rate is 76%, with a yearly death rate of 6%, 9%, and 9% in the first 3 years. Response, Philadelphia chromosome suppression, and survival were significantly better among patients in the low-risk category compared to intermediate- and high-risk categories, as defined by a multivariate analysis-derived prognostic model. The projected 3- year survival rate was 94% for patients who achieved a complete hematologic remission on interferon therapy and 45% for those who did not. Thirteen patients have developed blastic crisis, six with lymphoid and three with undifferentiated morphology. We conclude that human leukocyte alpha interferon effectively controls chronic myeloid leukemia and allows reappearance of diploid hemopoietic cells in some patients. 相似文献
103.
Phenotypic and functional characterization of T-BAM (CD40 ligand)+ T- cell non-Hodgkin's lymphoma 总被引:1,自引:0,他引:1
The precise mechanisms regulating T-helper function have been intensively investigated. We and others have recently identified a new T-cell-B-cell-activating molecule called T-BAM that directs B-cell differentiation by interacting with the CD40 molecule on B cells. Using a specific monoclonal antibody against T-BAM (5C8), we have previously shown that T-BAM expressing T cells are predominantly CD4+CD8- and in normal lymphoid tissue have a unique distribution. However, no information has been obtained regarding the phenotype and functional properties of human neoplastic T cells. Therefore, we investigated T- BAM expression immunohistochemically in 87 well-characterized T-cell non-Hodgkin's lymphomas and lymphoid leukemias (LL). We found that 21/81 neoplasms expressed detectable T-BAM and these positive tumors belong almost exclusively to the CD4+CD8- subtype. In addition, to determine whether T-BAM expression could be induced on T-BAM-LL cells, we activated T-BAM-LLs in vitro and showed that T-BAM could be upregulated only in CD4+CD8- tumors. Our studies clearly show that T- BAM is constitutively expressed in a large number of T-cell neoplasms with a relative mature phenotype (CD4+CD8-) and that only CD4+ neoplastic T cells can be induced in vitro to express this molecule. Additional studies are necessary to identify the biologic significance of T-BAM expression and its potential and clinical implications. 相似文献
104.
Parr RG Chen MB 《Proceedings of the National Academy of Sciences of the United States of America》1981,78(3):1323-1326
Circulant orbitals ϕn for a closed-shell system are the orbitals obtained when the N canonical orthonormal Hartree-Fock orbitals λ[unk] are subjected to a unitary transformation which is the discrete Fourier transformation: ϕn = 1/√N Σ[unk]λ[unk]ω(n-1)([unk]-1), where ω = exp(2πi/N). Electron densities associated with the orbitals ϕn are each close to the average total electron density. The Fock matrix, diagonal for canonical orbitals, for circulant orbitals is a Hermitian circulant matrix, εm, m+q = 1/N Σ[unk]ε[unk]ωq([unk]-1), where the ε[unk] are the canonical orbital energies. The states ^Fϕn are uniformly distributed on the surface of a sphere in Hilbert space. 相似文献
105.
Inhibition and complexation of activated protein C by two major inhibitors in plasma 总被引:5,自引:0,他引:5
To determine the major physiologic inhibitors of activated protein C (APC), plasma was incubated with APC or with Protac C and subjected to immunoblotting. APC:inhibitor complexes gave two major bands reacting with antiprotein C antibodies when immunoblotted on nondenaturing gels, and additional minor bands that varied between serum and plasma. Formation of one of the two major bands of APC:inhibitor complex, but not the other, was stimulated by heparin and only this band reacted with antibodies to the previously described APC inhibitor that is here designated PCI-1. Plasma immunodepleted of PCI-1 formed complexes with APC as visualized with antiprotein C but not anti-PCI-1 antibodies, and exhibited heparin-independent inhibition of APC activity, providing evidence for the existence of a second major physiologic APC inhibitor, PCI-2. Formation of APC:PCI-2 complexes in PCI-1-depleted plasma paralleled inhibition of APC amidolytic activity. PCI-2 was separated from PCI-1 and partially purified using column chromatography. PCI-2 formed inactive complexes of approximately 110,000 molecular weight (mol wt) with APC suggesting PCI-2 has an approximate mol wt of 50,000. Thus, inhibition of APC in plasma involves two major distinct 50,000 mol wt inhibitors, the heparin-dependent PCI-1 and the heparin- independent PCI-2. 相似文献
106.
March NH Parr RG 《Proceedings of the National Academy of Sciences of the United States of America》1980,77(11):6285-6288
For atoms and homonuclear diatomic molecules, it is argued that the electronic energies have the forms [Formula: see text] and [Formula: see text] [Formula: see text], respectively,where Z is the atomic number, N is the number of electrons, and R is the internuclear distance. By using the Lieb-Simon theorem that the Thomas-Fermi theory is exact in the limit of large atomic number and the Teller theorem that molecules are not bound in the Thomas-Fermi theory, it is then shown, among other results, that the electron-electron repulsion energy for neutral systems has no term in Z2 and that the nucleus-nucleus repulsion energy for neutral molecules is probably [unk](Z5/3). For neutral atoms, it is predicted and verified that the chemical potential (electronegativity) is [unk](Z-1/3) for large Z. Tetrahedral and octahedral molecules are briefly discussed. 相似文献
107.
Hardness, softness, and the fukui function in the electronic theory of metals and catalysis. 总被引:1,自引:2,他引:1 下载免费PDF全文
W Yang R G Parr 《Proceedings of the National Academy of Sciences of the United States of America》1985,82(20):6723-6726
The concepts of hardness eta = (2E/N2)nu and fukui function f(r) = [rho (r)/N]nu, which have recently been associated with the theory of chemical reactivity in molecules, are extended to the theory of metals. It is shown that at T = 0, 1/eta = g(epsilon F) and f(r) = g(epsilon F, r)/g(epsilon F), where g(epsilon F), and g(epsilon F, r) are the density of states and the local density of states, at the Fermi energy epsilon F. Softness S and local softness s(r) are defined as 1/eta and Sf(r), respectively, and it is shown that (formula; see text) where the averages are over a grand canonical ensemble. It is pointed out that the postulate that f(r) or g(epsilon F, r) determines site selectivity for metals in chemisorption and catalysis is synonymous with the recent argument by Falicov and Somorjai [Falicov, L. M. & Somorjai, G. A. (1985) Proc. Natl. Acad. Sci. USA 82, 2207-2211] that such selectivity is determined by low-energy density fluctuations. 相似文献
108.
Cardoso AA; Schultze JL; Boussiotis VA; Freeman GJ; Seamon MJ; Laszlo S; Billet A; Sallan SE; Gribben JG; Nadler LM 《Blood》1996,88(1):41-48
Even if neoplastic cells express tumor associated antigens they still may fail to function as antigen presenting cells (APC) if they lack expression of one or more molecules critical for the induction of productive immunity. These cellular defects can be repaired by physiologic activation, transfection, or fusion of tumor cells with professional APC. Although such defects can be repaired, antitumor specific T cells may still fail to respond in vivo if they may have been tolerized. Here, human pre-B cell acute lymphoblastic leukemia (pre-B ALL) was used as a model to determine if primary human tumor cells can function as alloantigen presenting cells (alloAPC) or alternatively whether they induce anergy. In the present report, we show that pre-B cell ALL express alloantigen and adhesion molecules but uniformly lack B7-1 (CD80) and only a subset express B7-2 (CD86). Pre-B ALL cells are inefficient or ineffective alloAPC and those cases that lack expression of B7-1 and B7-2 also induce alloantigen specific T- cell unresponsiveness. Under these circumstances, T-cell unresponsiveness could be prevented by physiologic activation of tumor cells via CD40, cross-linking CD28, or signaling through the common gamma chain of the interleukin-2 receptor on T cells. Taken together, these results suggest that pre-B ALL may be incapable of inducing clinically significant T-cell-mediated antileukemia responses. This defect may be not only due to their inability to function as APC, but also due to their potential to induce tolerance. Attempts to induce clinically significant antitumor immune responses may then require not only mechanisms to repair the antigen presenting capacity of the tumor cells, but also reversal of tolerance. 相似文献
109.
M. Inmaculada Poveda García M. Dolores del Pino y Pino Raquel Alarcón Rodriguez Cristian Rodelo-Haad Tesifón Parrón Carreño 《Nefrología : publicación oficial de la Sociedad Espa?ola Nefrologia》2019,39(1):67-72
Introduction
We aimed to assess the effectiveness of ambulatory blood pressure monitoring (ABPM) and subclinical target organ damage parameters for diagnosis of resistant hypertension (RH).Methods
We assessed demographic and anthropometric variables, the incidence of cardiovascular events and subclinical target organ damage (n = 112). We also studied the relationship between these variables and the ABPM results.Results
Of the 112 patients referred from primary care with a diagnosis of RH, 69 (61.6%) were confirmed by ABPM. We found statistically significant differences (P < .001) between patients with RH and pseudo-resistant hypertension in the appearance of subclinical target organ damage. A percentage of 84 of the patients had microalbuminuria: 66.25 ± 30.7 mg/dl); 44.9% had stage 3 chronic kidney disease: the average glomerular filtration was 59 ml/min/1.73 m2; and 56.5% had left ventricular hypertrophy on echocardiography. Fundoscopy revealed that 64% of the patients had hypertensive retinopathy. Three variables were associated with an increased HR risk: microalbuminuria, hypertensive retinopathy and left ventricular hypertrophy (OR 5.7, 6.2 and 11.2, respectively).Conclusions
This study shows that the systematic testing for target organ damage, particularly in terms of albuminuria, is a simple and inexpensive tool, with a high predictive value for RH (85%), which could be useful for prioritising patients who need ABPM. 相似文献110.
High incidence of monoclonal proteins in the serum and urine of chronic lymphocytic leukemia patients 总被引:2,自引:0,他引:2
Chronic lymphocytic leukemia (CLL) is generally considered a nonsecretory B cell immunoproliferative disorder. Conventional electrophoretic and immunoelectrophoretic methods have revealed serum monoclonal proteins in less than 10% of these patients. However, there is increasing experimental evidence from in vitro studies demonstrating that CLL cells may secrete immunoglobulins, particularly free light chains. We examined the serum and urine of 36 consecutive CLL patients for monoclonal proteins using sensitive immunochemical methods (high resolution agarose gel electrophoresis combined with immunofixation). The results obtained were correlated with the Rai stage, quantitative immunoglobulin levels, and lymphocyte membrane immunoglobulin phenotype of the leukemic cells. Twenty-three monoclonal proteins were identified in the serum or urine of 22 patients, an incidence of 61%. Six patients had serum monoclonal proteins, seven had only urinary monoclonal proteins, and nine had monoclonal proteins in serum and urine. In every instance the monoclonal protein was the same light chain type as expressed on the leukemic cells. Our findings suggest that the monoclonal proteins observed in the serum or urine of CLL patients are secretory products of the tumor cells and that their discovery is a function of the sensitivity of the method used for their detection. 相似文献